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2019 Spring Meeting



New strategies for smart biointerfaces

This symposium will bring together the diverse community of materials scientists, chemists, biologists and bioengineers focused on synthesis, characterization and design of smart biointerfaces. The most recent advances in fundamental studies, nano-bio material synthesis and biodevice design will be presented, offering unique opportunities for dissemination and synergy development.


Interfacial interactions between solid surfaces and biomolecules and cells underpin function and performance of materials in wide ranging applications, from implantable biodevices, to sensors, bioreactors and theranostic agents. Frontier research in this field focuses on achieving a deeper understanding of fundamental solid-bio interactions, while also on developing novel strategies for eliciting desirable bioresponses. Therefore, research in biointerfaces is cross-cutting and integrates multifaceted expertise in materials synthesis and modification, heterogeneous reactivity and charge transfer, nanoengineering, biochemistry, cell adhesion and biofilm regulation among others.

This symposium will bring together this diverse community of researchers to share progress on novel methodologies for the creation of smart biointerfaces with specific functionality and to disseminate the latest advances on our understanding of the solid-bio interface. Advanced methods for nanomaterial synthesis and modification have enabled new tools for regulating biomolecule conformation and cell adhesion at surfaces with nanoscale resolution through the control of topography, chemistry and morphology. Recent progress in selective surface modification of nanostructures, such as hot-spot functionalization, as well as the integration of tools from synthetic biology and electrochemistry have further contributed to our toolkit for the creation of tailor-made biointerfaces. Such progress in turn opens the door to the development of novel model systems for probing interactions of biomolecules, cells and tissues with solid materials, which are amenable to modelling via computational approaches, thus bridging the gap between theory and experiment. This symposium will explore synergies among these focal areas of research bringing together the latest advances in synthetic, device and modelling aspects of biointerfaces with the aim of catalysing the advent of the next generation of smart biomaterials.

Hot topics to be covered by the symposium:

The symposium will focus on the following themes in the area of biointerfaces:

  1. Nanostructured biointerfaces: including nano-bio, nanomedicine, nanoinstrumental characterization, nanoplasmonics
  2. Surface-cell interfaces and biofilms: including biofilm regulation, cell-electrode interfaces, bioelectrocatalysis, cell adhesion and proliferation at surfaces, smart antibacterial surfaces.
  3. Adaptive and responsive biomaterials: including smart polymers, stimuli responsive materials, controlled release, biosensing.
  4. Bioinspired materials: including functional biopolymer surfaces, supported biomimetic membranes, nano-biomolecule interface.
  5. Novel fabrication strategies for smart biointerfaces: including wetting modulation, bioconjugation, biosensing, bioactive functionality, array surface design.

List of invited speakers:

  • Matthew R. Lockett (Department of Chemistry, University of North Carolina at Chapel Hill, USA; confirmed): Healthy tissue to tumor models: using cellulose-based materials as scaffolds for 3D cell cultures
  • Nicolas Brun (Institut Charles Gerhardt Montpellier, France; confirmed): Enzymes at carbon electrodes: when porosity matters
  • Seiya Tsujimura (Division of Materials Science, Faculty of Pure and Applied Sciences; Univ. of Tsukuba, Japan; confirmed): Enzyme-based bioelectrocatalysis and its application to enzymatic biofuel.
  • Klaus Jandt (Institute of Materials Science and Technology (IMT); Friedrich Schiller University Jena, Germany, confirmed): Towards multifunctional and smart biointerfaces.
  • Lia Addadi (Department of Structural Biology; Weitzmann Inst. Israel, confirmed): Pending title.
  • Paolo Netti (Center for Advanced Biomaterials for Health Care; IIT - Istituto Italiano di Technologia, Italy, confirmed): Pending title.
  • Henk Busscher (Faculty of Medicine; University of Groningen, Netherlands, confirmed): Pending title


Selected papers will be published in the journal "Colloids and Surfaces B: Biointerfaces" (Elsevier).

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Functional Biointerfaces I : Paula Colavita
Authors : Klaus Jandt
Affiliations : Institute of Materials Science and Technology (IMT); Friedrich Schiller University Jena, Germany

Resume : Temporary text here.

Authors : Ezgi Bülbül, Dirk Hegemann, Manfred Heuberger
Affiliations : Empa, Swiss Federal Laboratories for Materials Science and Technology, Laboratory of Advanced Fibers, St. Gallen, Switzerland ETHZ Zurich, Department of Materials, Laboratory of Surface Science and Technology, Zurich, Switzerland

Resume : Frontier research in surface and biological sciences engage with a deeper understanding of mechanism associated with protein-surface interaction. To control molecular adsorption onto a surface one would consider altering surface properties. As a distinctive approach, we have elucidated the contribution of subsurface layers; the region buried several nanometres below the surface, to the protein adsorption via generating long-range interaction forces. Highly crosslinked, nanoporous subsurface vertical chemical gradient layers were designed by plasma polymerization. Based on hexamethyldisiloxane (HMDSO), the vertical gradient structure consists of a relatively thin, hydrophobic plasma polymerized HMDSO terminating layer on a thicker, hydrophilic plasma polymerized SiOx base. Moreover, an enhanced gradient was generated via post-oxidizing the base layer reducing the amount of residual hydrocarbon groups prior to depositing the terminating layer. We are able to detect the transition from hydrophobic to hydrophilic layer which corresponds to a thickness of 2-3 nm below the surface via angle resolved XPS and TofSIMS. The degree of water content upon hydration of such subsurface gradients was scrutinized using neutron reflectometry. Then, adsorption of bovine serum albumin (BSA) on dry and hydrated gradient layers was monitored using Transmission interferometric adsorption sensor (TInAS), which demonstrate that there is significant reduction in adsorbed BSA on hydrated gradient films as compared to reference samples. All the complementary techniques support that it is the oriented nanoconfined water accumulating in the subsurface which generates dipolar fields that remarkably modify protein-surface interaction.

Authors : Grazia M.L. Messina1, Benedetta Di Napoli3, Marta De Zotti2, Claudia Mazzuca3, Fernando Formaggio2
Affiliations : 1 Laboratory for Molecular Surfaces and Nanotechnology (LAMSUN), Department of Chemical Sciences, University of Catania and CSGI, Viale Andrea Doria 6, 95125, Catania, Italy; 2 Department of Chemical Sciences and Technologies, University of Roma Tor Vergata, Via della Ricerca Scientifica, 00133 Roma, Italy; 3 CB Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy

Resume : Materials that change structure and properties in response to different local stimuli are increasingly being studied in view of their potential application in the wide fields of nanosensors, molecular machines and/or bio-inspired nanotechnology. Peptides are ideally suited for this purpose because of the range of useful structural and chemical amino acid properties. Here we show the reversible conformational behavior driven by pH change of monolayers of Trichogin GA IV, a thiolated peptide belonging to the family of peptaibiotics, i.e., antimicrobial peptides rich in the helix-inducer ?-aminoisobutyric acid (Aib) residue, and its analog carrying Lys residues instead of Gly ones at positions 2, 5, 6, 9 (L1). In particular, the pH-driven response of L1 peptide monolayers involves the reversible loss/recovery of the monolayer mass and the parallel increase/decrease of its thickness, suggesting that a contraction/dilatation cycle of the monolayer is occurring. Experimental results, obtained by means of Quartz Crystal Microbalance with Dissipation monitoring (QCM-D), Surface Plasmon Resonance (SPR), Nano Plasmonic Sensing (NPS) technique, Fourier Transform Infrared - Reflection Attenuated Spectroscopy (FTIR-RAS) and Dynamic Force Spectroscopy (DFS), with Molecular Dynamics (MD) simulations provide detailed information on the overall monolayer structure and density with the pH changes, including the analysis of the intra- and inter-chain peptide dynamics, the structure of the peptide layer/water/solid interface as well as of the position and role of solvation and non-solvation water, i.e., highlighting an intriguing monolayer sponge-like behavior. Surprisingly, the reversible modification of mass and thickness, more than to the mere change of the peptide secondary structures, is rather due to pH-switched inter-chain aggregation modes, implying the massive and reversible expulsion of water from the monolayer. The present results may pave the way to critically reexamine the mechanism of stimuli-responsive systems.

Authors : V. Baldim1, N. Giamblanco2, A. Graillot3, N. Bia3, C. Loubat3, G. Marletta2, and J.-F. Berret*1
Affiliations : 1Matière et Systèmes Complexes, UMR 7057 CNRS Université Denis Diderot Paris-VII, Bâtiment Condorcet, 10 rue Alice Domon et Léonie Duquet, 75205 Paris, France. 2Laboratory for Molecular Surface and Nanotechnology (LAMSUN), Department of Chemical Sciences, University of Catania and CSGI, Viale A. Doria 6, 95125, Catania, Italy 3Specific Polymers, ZAC Via Domitia, 150 Avenue des Cocardie?res, 34160 Castries, France.

Resume : Nowadays, there is a need for coatings that can be applied to a broad range of surfaces and be supplied on a large scale. Herein, we use free radical polymerization to synthesize functional polymers, the objectives being to produce efficient coats for metal oxide particles and substrates. With nanoparticles of cerium, iron, titanium and aluminum oxide, we found that phosphonic acid PEG copolymers provide resilient coatings and long-term stability to the dispersions. In biological media, the particles are devoid of protein corona and do not aggregate. Using Quartz Crystal Microbalance, we address the issue of protein adsorption on flat iron oxide surfaces. We found that with PEGs of molecular weight of 5 kDa and of density 1 nm-2, the organic layer exhibits a protein resistance up to 99%. The present study establishes a correlation between the particle long-term stability in biological fluids and the protein resistance of flat coated substrates. The study suggests that the proposed coating allows controlling nanomaterial interfacial properties in biological environments. References G. Ramniceanu, B.-T. Doan, C. Vezignol, A. Graillot, C. Loubat, N. Mignet and J.-F. Berret, RSC Advances 6, 63788 ? 63800 (2016) N. Giamblanco, G. Marletta, A. Graillot, N. Bia, C. Loubat and J.-F. Berret, ACS Omega 2, 1309 ? 1320 (2017)

10:15 Coffee Break    
Bioinspired Materials and Interfaces : Klaus Jandt
Authors : Benjamin A. Palmer, Dvir Gur, Anna Hirsch, Gan Zhang, Dan Oron, Leeor Kronik, Leslie Leiserowitz, Steve Weiner, Lia Addadi
Affiliations : BA Palmer, D Gur, G Zhang, S Weiner, L Addadi, Dept. of Structural Biology, Weizmann Institute of Science; A Hirsch, L Kronik, L Leiserowitz, Dept. of Materials and Interfaces, Weizmann Institute of Science; D Oron, Physics of Complex Systems, Weizmann Institute of Science;

Resume : Organisms build complex and efficient optical devices including diffuse scatterers, broadband and narrow-band reflectors, tunable photonic crystals and concave segmented microscopic mirrors, and this is all about nano-interfaces. In the multilayer reflectors, light is reflected at periodic interfaces between specific organic crystals with high refractive index and cytoplasm, assembled inside specialized cells, the iridophores. The crystal constituent molecules that we know of are mostly limited to purines and pteridines. The crystal structure, the size, the morphology and the organization of the crystals are controlled from the nanoscale to the millimeter level. These devices perform a variety of optical functions, generating the white color of certain spiders, the metallic silvery reflectance of fish scales, the brilliant iridescent colors of some copepods, and mirrors used for vision in the eyes of scallops, crustaceans and fish. We are just starting to understand and rationalize the biogenic crystal structures and the superstructures in terms of the materials properties and the optical performance of the devices.

Authors : Abdon Pena-Francesch1, Melik C. Demirel2.3.4, Metin Sitti1
Affiliations : 1Physical Intelligence Department, Max Planck Institute for Intelligent Systems, 70569 Stuttgart, Germany; 2 Department of Engineering Science and Mechanics, Pennsylvania State University, University Park, PA, 16802, USA; 3 Center for Research on Advanced Fiber Technologies (CRAFT), Materials Research Institute, Pennsylvania State University, University Park, PA, 16802, USA; 4 Huck Institutes of Life Sciences, Pennsylvania State University, University Park, PA, 16802, USA

Resume : Recent research efforts have focused on developing soft, flexible, compliant materials for medical robotics, biointerfacing, and biosensing applications, with properties matching those of biological tissue. Because of their intrinsic softness, these materials are susceptible to cut, puncture, scratch, and/or tear damage that compromises the physical integrity of the device/interface. Soft self-healing materials offer a solution to this challenge and improve the long-term reliability, although many of the commonly explored self-healing chemistries are not biocompatible and are time-consuming (healing times often longer than 24 hours). To overcome these problems, we present biocompatible synthetic protein-based materials, inspired in squid proteins, that self-repair microscopic and macroscopic damage within seconds. The self-healing mechanism relies on the formation of ?-sheet nanostructures (2-3 nm) that act as reversible crosslinks in an elastomeric protein network. The healing process takes place in physiological conditions and the mechanical properties are recovered after healing (up to 200% and 25 MPa). Furthermore, the protein material can be functionalized with biomolecules such as enzymes that maintain their activity after several healing cycles. These protein-based self-healing materials find applications as adaptive actuators for soft robotics, dependable biosensing platforms, and protective textiles against chemical and biological warfare agents.

Authors : Francesca Biscaglia, Gianfranco Bocchinfuso, Antonio Palleschi, Marina Gobbo, Moreno Meneghetti
Affiliations : Francesca Biscaglia, Marina Gobbo, Moreno Meneghetti Department of Chemical Sciences?, University of Padova, ?Via Marzolo 1, 35131 Padova, Italy Gianfranco Bocchinfuso, Antonio Palleschi Department of Chemical Sciences & Technologies, University of Roma Tor Vergata and CSGI?, Via della Ricerca Scientifica, 00133 Rome, Italy

Resume : The control over cell targeting with nanostructures is an important issue in diagnosis, imaging and targeted therapy. Targeting can be obtained linking bioactive molecules to the nanostructures. Activity of small molecules on nanostructures can be increased because of their large number on nanostructures (avidity effect). However, specificity and sensitivity not always can be increased in particular because of non specific interactions. We will show how peptides have to be engineered to achieve both good specificity and sensitivity of functionalized plasmonic nanostructures. In particular we will show results obtained with the peptide GE11, which is active against the Epidermal Growth Factor Receptor (EGFR) [1]. SERS will be used for the experimental measurement of the activity. Molecular dynamics calculations guide the interpretation of the experimental results showing the arrangement of the peptides on the surface of the nanostructures and justifying their activity. Other results will be reported for other peptides on plasmonic nanostructures, which show how a strategy for the engineering of the peptide can be found. 1. Francesca Biscaglia, Senthilkumar Rajendran, Paolo Conflitti, Clara Benna, Roberta Sommaggio, Lucio Litti, Simone Mocellin, Gianfranco Bocchinfuso, Antonio Rosato, Antonio Palleschi, Donato Nitti, Marina Gobbo, and Moreno Meneghetti, Enhanced EGFR Targeting Activity of Plasmonic Nanostructures with Engineered GE11 Peptide, Adv. Healthcare Mater. (2017) 1700596.

Authors : Dr. Indranath Chakraborty, Prof. Dr. Wolfgang J. Parak
Affiliations : Fachbereich Physik and Center for Hybrid Nanostructure (CHyN), Universität Hamburg, 22761 Hamburg, Germany.

Resume : Abstract: Tuning nanoparticles surfaces is very important to introduce new properties to the system such as solubility, self-assembly, sensing, biocompatibility, etc.1,2 This talk will explain how proteins were used as shape controlling agents for different Ag and Au NPs in a sustainable way. For the case of silver, the shape of the resulting nanoparticles could be tuned by the selection of the types of proteins.3 The number of accessible lysine groups was found to be mainly responsible for the anisotropy in nanoparticle formation. On the other hand, gold produced similar morphology irrespective the types of proteins used. The method can be scaled up and liters of NP can be prepared in a single batch. Structural change in protein was also evaluated in detail. Protein protected NPs have shown promising colloidal stability as well as biocompatibility and also, some of them can be used in potential applications such as glutamate sensing.4 Reference: (1) Chakraborty, I.; Pradeep, T. Atomically Precise Clusters of Noble Metals: Emerging Link between Atoms and Nanoparticles. Chem. Rev. 2017, 117 (12), 8208. (2) Hühn, J.; Carrillo-Carrion, C.; Soliman, M. G.; Pfeiffer, C.; Valdeperez, D.; Masood, A.; Chakraborty, I.; Zhu, L.; Gallego, M.; Zhao, al. Selected Standard Protocols for the Synthesis, Phase Transfer, and Characterization of Inorganic Colloidal Nanoparticles. Chem. Mater. 2017, 29, 399?461. (3) Chakraborty, I.; Feliu, N.; Roy, S.; Dawson, K.; Parak, W. J. Protein-Mediated Shape-Control of Silver Nanoparticles. Bioconjugate Chem. 2018, 29, 1261. (4) Zeng, Y.; Chang, Y.-H.; Gharib, M.; Parak, W. J.; Chakraborty, I. Understanding the Interaction of Glutamate Salts with Serum Albumin Protected Prism-Shaped Silver Nanoparticles toward Glutamate Sensing. Particle & Particle Systems Characterization 2019, 0 (0), 1800229.

Authors : Lucia Podhorska [1], James C. McCormack [1], Shauna P. Flynn [1], Niamh Hunt [2], Christine Loscher [2] and Susan M. Kelleher [1]
Affiliations : [1] School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland; [2] School of Biotechnology, Dublin City University, Glasnevin, Dublin 9, Ireland

Resume : Many cellular functions are governed by chemical and physical mechanisms that occur on the nanoscale, therefore being able to emulate the submicron scale structures that cells interact with is crucial if one is to induce desirable cellular behaviour in vitro. By combining nanolithography and soft lithography methods, we produce surfaces patterned with such high-resolution nanostructures. This is achieved via block copolymer micelle lithography (BCML), a versatile tool for producing nanopatterned silicon surfaces. By taking advantage of the ability of the micelle core to form complexes with metal ions, it is possible to fabricate surfaces with precisely-tuned regularly-spaced nanoparticles, which can act as masks for plasma etching, thus transferring the desired features into the underlying substrate. By implementing gold and iron oxide nanoparticles as hard masks, we have created surfaces with nanoneedles of controlled diameter (30-55 nm), pitch (95-330 nm) and height (45-100 nm). A subsequent replica moulding process developed within the group allows us to re-create these features using a range of polymers. In this way we are working to fully reproduce naturally occurring nanostructures, such as those found on insect wings. [1] We are mimicking these structures and properties on silicon and polymers, using the experimental methods outlined above, in order to investigate their cytotoxicity and ability to penetrate the cell membrane. [1] Appl. Mater. Interfaces 8 (2016) 14966

12:00 Lunch    
Functional Biointerfaces II : Francois Berret
Authors : Daniel Crespy
Affiliations : Vidyasirimedhi Institute of Science and Technology (VISTEC)

Resume : Release of appropriate amounts of drugs at targeted locations of the body is crucial for therapies based on drug delivery. Drugs can be released upon degradation or swelling of the polymer matrix of nanoparticles or through the cleavage of labile bonds [1]. We recently created a new type of cleavage linkage on polymers, called hemiaminal ether group, that can be used to deliver drugs from polymer conjugates in a sustained manner in mild acidic conditions [2]. Furthermore, to increase the selectivity of redox-responsive nanocapsules system, we encapsulated a synthesized prodrug in porous silica nanocontainers [3]. The prodrug could not diffuse through the shell on non-reductive conditions and release. On the contrary, drug release occurred when the prodrug was cleaved in reductive conditions, leading to the formation of small drug molecules that could permeate through the nanocapsules shell. The various approaches have advantages and drawbacks that are discussed in the frame of this presentation. References [1] Seidi, F.; Jenjob, R.; Crespy, D. Chem. Rev. 2018, 118, 3965 [2] Seidi, F.; Druet, V.; Huynh, N.; Phakkeeree, T.; Crespy, D. Chem. Commun. 2018, 54, 13730 [3] Behzadi, S.; Steinmann, M.; Estupinan, D.; Landfester, K.; Crespy, D. J. Contr. Rel. 2016, 242, 119 [4] Behzadi, S.; Rosenauer, C.; Kappl, M.; Mohr, K.; Landfester, K.; Crespy, D. Nanoscale 2016, 8, 12998

Authors : Giovanni Li Destri, Grazia M.L. Messina, Nunzio Tuccitto, Giovanni Marletta
Affiliations : Laboratory for Molecular Surfaces and Nanotechnology (LAMSUN), Department of Chemical Sciences, University of Catania and CSGI, Viale Andrea Doria 6, 95125, Catania, Italy

Resume : We report a new strategy, based on metal cation chelation processes, to promote site-specific immobilization of proteins at solid interfaces. The approach implies the formation of a mercaptoundecanoic acid monolayer on a gold surface, which is then activated to covalently bind the GHK tripeptide, exploited to coordinate Cu(II) ions and providing a selective platform for site-specific immobilization of Human Serum Albumin (HSA). HSA anchoring on the chelating surfaces was followed by quartz crystal microbalance with dissipation monitoring and force spectroscopy technique. Changes in frequency and dissipation, as well as the corresponding D-f plot and HSA antibody adsorption experiments, reveal the driving effect of the chelating sites on the protein conformation, also confirmed by force spectroscopy results, showing the change in the conformational state of the anchored proteins respectively on chelating and non-chelating surfaces. The protein immobilization process has been rationalized in terms of an extended Random Sequential Adsorption model with variable protein footprints, enabling the correct simulation of the experimentally measured protein average surface coverage as a function of the surface structure and, additionally, supporting the promotion of different interfacial conformations of the proteins anchored on the two types of surfaces.

Authors : Shahrzad Shadman Yazdi, Tung Nguyen-Dang, Tapajyoti Das Gupta, Ines Richard, Prof. Fabien Sorin
Affiliations : Laboratory of Photonic Materials and Fiber Devices (FIMAP) Institute of Materials Ecole Polytechnique Federale de Lausanne (EPFL) Lausanne 1015, Switzerland

Resume : The interest in biodegradable parenteral drug delivery systems is steadily rising in modern therapeutics. In particular, the development of a sustained multi-dose drug delivery device in a fiber form can bring novel opportunities in biomedical applications such as sutures, scaffolds, orthopedic implants, and wound dressings. Thus far however, the fabrication of micro-structured multi-material biodegradable fibers remains complex and challenging. Here we demonstrate the thermal drawing of biodegradable thermoplastic polymers with tailored microstructures. We first fabricate fibers with a simple architecture thanks to which the release property of the thermally drawn polymers is studied via fluorescence spectroscopy and scanning electron microscopy (SEM). Based on this analysis, complex fibers, with partially or fully biodegradable compositions, are developed which are capable of releasing drugs at prescribed times and with controlled dosages. Furthermore, tensile tests of biodegradable fibers reveal mechanical properties suitable for a variety of applications in the field of drug release, which further highlights the unique attributes of the thermal drawing process to generate highly functional biodegradable fibers. Opportunities for a variety of drug release systems in biomedical and personalized care applications will be discussed.

Authors : Larisa Florea
Affiliations : AMBER, School of Chemistry, Trinity College Dublin

Resume : Herein we employ Direct Laser Writing (DLW) by Two-Photon Polymerisation (2PP) as a new route towards the creation of 3D soft polymeric assemblies that possess responses akin to biological systems, in particular the ability to alter physical characteristics in response to an external stimulus. A wide range of soft stimuli-responsive 3D structures have been fabricated by DLW with sub-micron resolution. These soft 3D structures absorb considerable quantities of solvent to produce impressive stimuli-response.[1] Directed movement in 3D was achieved through the programmed design of the 3D structure itself, via precise control of the polymer density inside the structure. This endo-skeletal internal framework allowed for directed motion to be encoded in the 3D structure. 1. L. Florea, et al. Materials Today 21.8 (2018): 807-816.

Affiliations : 1. HONGSIK CHAE (Department of Materials Science and Engineering, Seoul National University, Seoul 08826, Korea) 2. DONG-KYU KWAK (Disease Target Structure Research Center, KRIBB, Daejeon 34141, Korea) 3. MI-KYUNG LEE (Disease Target Structure Research Center, KRIBB, Daejeon 34141, Korea) 4. SEUNG-WOOK CHI* (Disease Target Structure Research Center, KRIBB, Daejeon 34141, Korea) 5. KI-BUM KIM* (Department of Materials Science and Engineering, Seoul National University, Seoul 08826, Korea)

Resume : Although protein?protein interactions (PPIs) are emerging therapeutic targets for human diseases, development of high-throughput screening (HTS) technologies against PPI targets remains challenging. In this study, we propose a protein complex structure to effectively detect conformational changes of protein resulting from PPI using solid-state nanopore for a novel, widely-applicable drug screening method against various PPI targets. To effectively detect conformational changes resulting from PPI, we designed a fusion protein MLP (MDM2-linker-p53TAD), where p53TAD and MDM2 are connected by a 16 amino acid linker. The globular conformation of MLP exhibited a single-peak translocation event, whereas the dumbbell-like conformation of nutlin-3-bound MLP revealed as a double-peak signal. The proportion of double-peak to single-peak signals increased from 9.3% to 23.0% as nutlin-3 concentration increased. The translocation kinetics of the two different MLP conformations with varied applied voltage were analyzed. Further, the fractional current of the intra-peak of the double-peak signal was analyzed, probing the structure of our designed protein complex. This approach of nanopore sensing may be extendedly employed in screening of PPI inhibitors and protein conformation studies.

Authors : Carli Stefano, Fadiga Luciano, Biscarini Fabio
Affiliations : Center for Translational Neurophysiology of Speech and Communication Istituto Italiano di Tecnologia 44121 Ferrara (Italy)

Resume : One of the main concern related to chronically implanted neural interfaces is related to the adverse reaction of the surrounding tissue, which is known to encapsulate the neural microelectrodes after few weeks post implantation, leading to the loss of neural recording/stimulating activity. With the aim to minimize this inflammatory reaction, the potent glucocorticoid dexamethasone-phosphate (DEX-P) can be locally delivered from poly(3,4-ethylenedioxythiophene) (PEDOT) based drug delivery systems electrodeposited on neural implants. It is known that the use of DEX-P as a dopant negatively affects the electrochemical properties of the resulting PEDOT/DEX-P films. In order to circumvent this disadvantage dexamethasone (DEX) was covalently bound to PEDOT, thereby enabling a biochemically triggered drug release system based on the hydrolysable bond between DEX and PEDOT. Furthermore, the neuroprotective natural bile acid Tauroursodeoxycholic acid (TUDCA) was incorporated within PEDOT through the ionic approach, leading to the new PEDOT-TUDCA composite material that can actively deliver the drug upon electrochemical activation. Impedance spectroscopy confirmed the improved electrochemical properties of PEDOT-DEX and PEDOT-TUDCA with respect to classic PEDOT/DEX-P films. In conclusion, we furnish two new alternative to the classic incorporation of DEX-P in PEDOT based drug delivery systems that may be suitable for long lasting neural recording/stimulation studies.

Authors : B.Di Napoli, C.Mazzuca, M.De Zotti,F.Formaggio, M. Venanzi, A.Palleschi
Affiliations : B.Di Napoli, C.Mazzuca, M. Venanzi, A.Palleschi: Department of Chemical Science and Technology, University of Rome ?Tor Vergata?, Via della Ricerca Scientifica, 00133, Rome, Italy; M.De Zotti, F.Formaggio: CB Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy

Resume : A detailed characterization of the behavior of peptides at the air/water interface, in terms of the influence of the peptide concentration on its conformations and on the final film structure is a less examined matter, even if the formation of peptide monolayers is a well established experimental procedure. In this regard, two short helical peptides, the amphiphilic Trichogin GA IV and the hydrophobic Z-(Aib)9-OtBu, have been studied by means of molecular dynamic simulations of their Langmuir-Blodgett compression isotherms. We show that, due to compression, different structural changes occur: initially formed drop-like aggregates coalesce forming nanofibers, constituting a web-like structure (surrounding water pools) on increasing the surface tension. During these transitions, peptidic chains lie almost parallel to the surface mostly adopting a helical conformation. At high peptide concentration, a monolayer of peptides in a vertically aligned disordered conformation is formed. All the results allow to characterize the formation of the peptides monomolecular films highlighting their features.

Poster Session I : TBD
Authors : Anita Visan1, Carmen Ristoscu1, Gianina Popescu-Pelin1, Mihai Soprony1, R. Cristescu1, Carmen Mariana Chifiriuc3, David Grossin4, Fabien Brouillet4, Ion N. Mihailescu1
Affiliations : 1 National Institute for Lasers, Plasma and Radiation Physics, Magurele, Ilfov, Romania ; 2 National Institute of Materials Physics, Magurele, Ilfov, Romania;3Department of Microbiology, Faculty of Biology, University of Bucharest, 060101; Research Institute of the University of Bucharest –ICUB, Spl. Independentei 91-95, Bucharest, Romania;4 CIRIMAT – Carnot Institute, University of Toulouse, ENSIACET; 4 Allée Emile Monso, 31030 Toulouse Cedex 4, France

Resume : Antimicrobial chitosan-biomimetic nanocrystalline apatite –tetracycline coatings were deposited by Matrix Assisted Pulsed Laser Evaporation technique with a KrF* excimer laser source was used (λ = 248 nm, ζFWHM ≤ 25 ns). FTIR spectra of the obtained thin films were found to be highly similar to the spectrum of the initial powders. Scanning electron microscopy evidenced a typical morphology characteristic to deposition technique, advantageous for envisaged application, the nanoscale roughness increasing with the chitosan concentration. We evaluate the antibacterial properties of a thin coating containing chitosan and tetracycline deposited by MAPLE on titanium samples, using as model organisms the Gram-negative E. coli and the Gram-positive E. faecalis. The biocompatibility of the obtained films deposited on Ti substratum was evaluated in vitro on human bone osteosarcoma cells, by investigating the morphology and cellular cycle of the cells growing on the obtained thin films. The results demonstrated that the chitosan - biomimetic nanocrystalline apatite-tetracycline composite coatings improve bone formation and facilitate anchorage between the bone and the prosthesis validating the method used.

Authors : J. Szewczenko, W. Kajzer, A. Kajzer, M. Basiaga, M. Kaczmarek, R. Major, J. Jaworska, K. Jelonek, P. Karpeta-Jarzabek, J. Kasperczyk,
Affiliations : J. Szewczenko; W. Kajzer; A. Kajzer; M. Basiega; M. Kaczmarek - Department of Biomaterials and Medical Devices Engineering, Faculty of Biomedical Engineering, Silesian University of Technology, Zabrze, Poland. R. Major - Institute of Metallurgy and Materials Science of Polish Academy of Sciences, Kraków, Poland J. Jaworska; K. Jelonek; P. Karpeta-Jarzabek; J. Kasperczyk - Centre of Polymer and Carbon Materials of the Polish Academy of Sciences Zabrze, Poland.

Resume : The paper presents the results of research on the influence of surface topography and wettability of the Ti6Al7Nb alloy on the adhesion of the PLGA coating. The surface of the alloy was modified using a mechanical pre-treatment including: grinding, vibratory processing, mechanical polishing, sandblasting and anodic oxidation. The polymer coating was applied to by immersion. The scope of research included microscopic observations using SEM and acoustic microscopy of the substrate and polymer coating. In addition, investigations were carried out on wettability and surface topography of the polymer coating and metal substrate, the polymer coating thickness as well as qualitative and quantitative studies on the adhesion of the polymer coating to the substrate. Adhesion tests were carried out on the samples at the initial state and after 6 weeks exposure to Ringer's solution. The analysis of the results indicates the influence of the method used to modify the metal substrate on its topography and wettability. These parameters affect the thickness of the polymer coating produced. Regardless of the metal substrate parameters, qualitative analysis of adhesion of the coating applied to the Ti6Al7Nb alloy substrate showed no delamination for both samples exposed to and not exposed to Ringer's solution. In contrast, the quantitative scratch-test showed different adhesion of the polymer coating depending on the surface topography obtained by various modification methods. Acknowledgments: The work is the result of the research project. 2015/19 / B / ST5 / 03431 funded by the National Science Center.

Authors : Ji-sun Park, Tea-gon Jung, Yong-hoon Jeong, Jae-young Jeong, Jae-Woong Yang, Kwang-Min Park, Kwan-Su Kang, Jae-young Lee, Su-a Park
Affiliations : Department of R&D, Osong Medical Innovation Foundation Medical Device Development Center, Gwangju Institute of Science and Technology, Korea Institute of Machinery & Materials

Resume : Three dimensional (3D) bio-printing techniques, which can fabricate 3D porous structures with good environment for cell growth, have been attracting much attention for various biomedical applications in tissue engineering field. To this end, bioink materials able to offer good printability and favorable cellular interaction are highly required. Herein, we synthesized alginate sulfate, which is a structural mimic of heparin that can strongly bind with growth factors owing to form surface charge effect to prolong their activities, and studied its feasibility for cell printing applications. Several bio-inks composed of alginate and alginate-sulfate were studied to characterize their material properties and their utilities in 3D printing. The inclusion of alginate-sulfate in bio-inks (alginate/alginate-sulfate) did not significantly influence their rheological properties and allowed for a good 3D printing processibility with distinct pores and features. Moreover, alginate/alginate-sulfate bio-inks exhibited an improved retention of bone morphogenetic protein 2 in 3D-printed scaffolds. Osteoblastic proliferation and differentiation in vitro were promoted by alginate/alginate-sulfate 3D-printed constructs with an optimal composition of 3% alginate and 2% alginate-sulfate. We envision that bio-inks displaying prolonged interactions with growth factors will be useful for tissue engineering applications including bone regeneration. Keywords 3D printing; Alginate; Bone morphogenetic protein (BMP); Bone tissue engineering; Biomaterials

Authors : Shen-Jun Yuan 1, Yu Wen 1, Li Zhao 2, *, Xiao Chen 1, *
Affiliations : 1 Department of Pharmacology, School of Basic Medical Sciences, Wuhan University, Donghu Avenue No.185, Wuhan, 430071, China 2 School of Radiation Medicine and Protection & School for Radiological and Interdisciplinary Sciences (RAD-X), Soochow University, Suzhou, 215123, China

Resume : Numerous nano devices have been reported for targeted delivery of chemotherapeutic agents in malignant tumors. However, whether a drug in nano form acts to the same effects as the free drug remains mostly overlooked. Moreover, the nano drug?s efficacy in relation to the tumor associated macrophages (TAM), which are key components of the tumor stroma, is also a question largely unanswered. In our work to look into these questions, chemotherapeutic agent cisplatin (Pt) in the form of quadrivalent platinum was loaded to polyglycerol-coated carbon dots conjugated with glucose as targeting moiety, yielding carbon dot-glucose-platinum composites (CD-Glu-Pt). In-vitro experiments showed preferential uptake and toxicity of CD-Glu-Pt in human breast cancer cells (MCF-7) over umbilical vein endothelial cells (HUVEC) and CD-Glu-Pt?s toxicity to the cancer cells could not be blocked by glucose. TAM with a type-2 activation phenotype were found to take up CD-Glu-Pt and tolerate both CD-Glu-Pt and Pt. In-vivo experiments subsequently demonstrated CD-Glu-Pt?s targeted anti-cancer efficacy and reduced systemic toxicity relative to Pt. Importantly, TAM were shown to protect against the anti-tumor effects both of CD-Glu-Pt and Pt. Next, CD-Glu-Pt were found to induce autophagy in the cancer cells, in contrast to apoptosis induced by Pt while both CD-Glu-Pt and Pt caused emission of damage associated molecular patterns (DAMPs) from the cancer cells. Finally, TAM failed to be reprogrammed into an inflammatory phenotype in the presence of cancer-cell derived DAMPs. Taken together, these data suggest that 1) carbon dots conjugated with glucose may serve as an effective tumor-targeting delivery platform; 2) a targeted delivery device may have distinct cellular and therapeutic responses from the drug it is meant to deliver; and 3) their therapeutic efficacy could be modulated by the TAM.

Authors : Maria Chiara Sportelli (1,2), Margherita Izzi (1), Annalisa Volpe (2), Valentina Lacivita (3), Maurizio Clemente (1), Rosaria Anna Picca (1), Cinzia Di Franco (2), Amalia Conte (3), Matteo Alessandro Del Nobile (3), Antonio Ancona (2), Nicola Cioffi (1)
Affiliations : (1) Department of Chemistry, University of Bari “Aldo Moro”, Via Orabona, 4, 70126 Bari, Italy; (2) CNR, Istituto di Fotonica e Nanotecnologie UOS Bari, Physics Department, Via Amendola, 173, 70126 Bari, Italy; (3) Department of Agricultural Sciences, Food and Environment, University of Foggia, Via Napoli, 25, 71121 Foggia, Italy;

Resume : The development of bioactive metals with controlled ion release, which allows having a noteworthy antimicrobial activity associated with low toxicity to humans, is one of the major challenges in the scientific community [1]. These materials have opened new horizons in the searching of alternative routes to fight bacterial resistance towards conventional antibiotics and disinfecting agents. In this work, nanocomposites based on polyethylene oxide (PEO) and copper nanoparticles (CuNPs) were developed as new active packaging for fresh foodstuffs. In the last years, indeed, the use of other metals, besides the well-known silver and gold, as antimicrobial agents in this field is growing [2], with the purpose to reduce production costs. Copper colloids were synthesized by femtosecond-pulsed laser ablation synthesis in solution (LASiS) using an organic environment, to ensure a good solubility of nanocolloids in polymeric solution. CuNPs were incorporated in a biodegradable polymer matrix for the preparation of composite films. Nanocolloids and composites were morphologically and spectroscopically characterized and bioactive ions release over time from composite films was studied by atomic absorption spectroscopy. Finally, shelf life test on fresh-cut fruit was carried out to assess the effects of nanocomposite systems on product quality. [1] M.C. Sportelli et al., TrAC 84 (2016) 131–138 [2] C. Costa et al., Ch. 31 in “Antimicrobial Food Packaging” (2016), pp. 399–406, J. Barros-Velázquez (Ed.), San Diego: Academic Press.

Authors : Raj Kumar, Orit Shefi, Amit Sitt
Affiliations : Bar Ilan Institute of Nanotechnology and Advanced Materials (BINA) and Faculty of Engineering, Bar Ilan University, Ramat Gan-5290002 Israe School of Chemistry, Sackler Faculty of Exact Sciences, Tel Aviv University, Tel Aviv, 6997801 Israel

Resume : There is a growing need for biocompatible nanocomposites that will effectively interact with biological tissues through multiple modalities. However, many new synthesised nanomaterials are limited their use in neural tissue engineering application due to higher cytotoxicity. Hence, synthesis of new materials with good biocompatibility and biodegradability is always in demand for tissue engineering applications. we studied various materials such as gold nanoparticles, silver nanoparticles coated substrates to promote neural differentiation and outgrowth. however, it is two dimensional. Various researchers developing the three-dimensional tissue engineering scaffold such as a hydrogel. However, hydrogel has its own disadvantages and limited to the number of hydrogels only available. There is high demand for the materials to control the direction of neuron regeneration. Hence, tubes like nanomaterials are an emerging source for neural tissue engineering application. Here, we synthesise the PLGA-PEG microtubes with controlling physicochemical properties. The interaction of polymeric mirotubes is investigated with neuronal cells. We studied the cell viability and differentiation of PC12 cells and SH-SY5Y cells. Results showed good biocompatibility and excellent interaction with cells. Controlling direction of regenerating neurons through micrtubes are the promising application in peripheral nerve regenerations. Hence, these microtubes can be serve as scaffold for neural tissue engineering

Authors : Raj Kumar, Orit Shefi, Yogendra Kumar Mishra
Affiliations : Bar-Ilan Institute for Nanotechnology and Advanced Materials (BINA) and Faculty of Engineering, Bar-Ilan University, Ramat Gan 5290002, Israel Functional Nanomaterials Center, Institute of Materials Science, Kiel University, Kaiserstr, 2, D-24143 Kiel, Germany

Resume : There is a growing need for biocompatible nanocomposites that will effectively interact with biological tissues through multiple modalities. However, many new synthesised nanomaterials are limited their use in neural tissue engineering application due to higher cytotoxicity. Hence, synthesis of new materials with good biocompatibility and biodegradability is always in demand for tissue engineering applications. we studied various materials such as gold nanoparticles, silver nanoparticles coated substrates to promote neural differentiation and outgrowth. however, it is two dimensional. Various researchers developing the three-dimensional tissue engineering scaffold such as a hydrogel. However, hydrogel has its own disadvantages and limited to the number of hydrogels only available. Hence, three-dimensional nanomaterials are an emerging source for neural tissue engineering application. Here, we synthesise the ZnO tetrapods microstructures with controlling physicochemical properties. The interaction of zinc oxide tetrapods is investigated with neuronal cells. We studied the cell viability and differentiation of PC12 cells and SH-SY5Y cells. Results showed good biocompatibility and excellent interaction with cells. Controlling organization of Zinc oxide tetrapods structures can be a promising material for 3D neural network outgrowth and scaffold for neural tissue engineering.

Authors : Caio H. N. Barros, Henry Devlin, Stephanie F. Fulaz Silva, Dishon W. Hiebner, Laura Quinn, Stefania Vitale, Eoin Casey
Affiliations : School of Chemical and Bioprocess Engineering - University College Dublin - Ireland

Resume : Biofilms are microbial aggregates embedded in a self-produced Extracellular Polymeric Matrix (EPS) that provides nutrients and physical resilience to the microbial community. Because of their lower susceptibility to antimicrobials, biofilms are often problematic due to their formation in industrial environments and in biomedical contexts. The search for new anti-biofilm approaches includes those from the field of nanotechnology, and the use of nanoparticles (NPs) has emerged as a valuable tool for biofilm matrix probing and/or dispersion. However, for an effective utilization of NPs in anti-biofilm methodologies more information is needed regarding EPS-NP interactions. This study involved the synthesis of different functionalized silica NPs and the cultivation of P. fluorescens biofilms for EPS extraction. Given that proteins are a major constituent of these biofilms, and they are known to form a corona around NPs in biological media, the bio-nano interactions were assessed by exposing the nanoparticles to the extracted EPS, followed by analysis of protein corona using SDS-PAGE and LC-MS/MS experiments. Differences were observed in the protein attachment profiles onto particles with distinct chemical functionalities, and the data correlate with the ones seen in Confocal Microscopy studies of in vivo biofilms exposed to the NPs. The outcome of this study provides relevant insights in the area of biofilm-nanoparticle interactions.

Authors : Alina Maria Holban1,2*; Lia-Mara Ditu2; Alexandru Mihai Grumezescu1; Carmen Curutiu2; Coralia Bleotu3; Valentina Grumezescu4; Veronica Lazar2, Bogdan Vasile1; Ecaterina Andronescu1
Affiliations : 1 Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Romania; 2 Faculty f Biology, University of Bucharest, Romania; 3 Ştefan S. Nicolau Institute of Virology, Bucharest, Romania; 4 Laser-Surface-Plasma Interactions” Laboratory, Lasers Department, National Institute for Lasers, Plasma and Radiation Physics, Magurele, Romania

Resume : Recent studies report the utility of nanoparticles (NPs) to fight resistant infections. However, NPs may also impact on the gut microbiota, which is exposed to many products which contain NPs and also orally administered therapeutics. The aim of this study was to evaluate the impact of functional core-shell magnetite NPs on the growth and virulence of opportunistic (Staphylococcus aureus, Pseudomonas aeruginosa) and microbiota (Enterococcus faecalis, Lactobacillus rhamnosus) isolates. NPs were obtained by co-precipitation in polyethylene glycol solution, followed by tetraethoxysilane to obtain core-shell structures. Characterization was done by transmission electron microscopy, scanning electron microscopy, infrared, X-ray diffraction and thermogravimetric analysis. Antimicrobial effect was tested by qualitative and quantitative methods, attachment by modified Cravioto method using human cultured cells and biofilms were assessed by microtiter approach. Results demonstrated that tested NPs have uniform sphere shape, ranging 20-25nm in diameter and showed different minimum inhibitory concentrations, depending on the tested strain, their antimicrobial effect being more obvious against Gram positive strains. NPs significantly inhibited the attachment to cellular substrata of the pathogenic strains (more than 50%), while attachment modulation in the microbiota strains was lower (~ 10%). Biofilm formation was differently modulated in pathogenic and microbiota strains. Results demonstrate that core-shell magnetite nanoparticles may differently impact on the growth and virulence of pathogenic and microbiota microbial species, the most significant differences being observed in their ability to attach and produce biofilms.

Authors : Graham M. Reid (1), Lucia Podhorska (1), (1) Shauna P. Flynn, Laura Quinn (2), Eoin Casey (2), Susan Mulansky (3), Susan M. Kelleher (1)
Affiliations : (1) School of Chemistry, University College Dublin; (2) School of Chemical and Bioprocess Engineering, University College Dublin; (3) Institute of Food and Biochemical Engineering, Technische Universität Dresden

Resume : The nanostructured topography of cicada wings has been shown to possess antibacterial properties. Although the bactericidal action is not fully understood it has been shown to be based on the physical surface structure, making it an attractive route for controlling antibiotic resistant strains. There is an opportunity to fabricate nanostructured materials that maintain the bactericidal activity of the insect wing and gain a better understanding of the mode of action of these surfaces and how to best fabricate the structure to effectively promote cell death. Our group is interested in producing nanostructured polymeric materials which could have applications in the coating of surfaces in a medical or food setting. We have used block copolymer lithography to transfer a nanopattern to a Si substrate. Our cylinder forming poly (styrene - block - methyl methacrylate) polymer is thermally annealed over a neutral brush layer to microphase separate into perpendicular cylinder domains of 20 nm in diameter, with a spacing of 40 nm. Using UV irradiation to remove the polymethyl methacrylate cores facilitates the backfilling of an Fe(NO3)3 hard mask. An oxidation step of the Fe(NO3)3 produces a final iron oxide hard mask that allows plasma etching of the underlying Si, producing a master template of hexagonally packed pillars that are then moulded in a specialised molding chamber using UV-curable polymers to produce nanopatterned polymer surfaces. The nanostructured silicon, and the corresponding polymer surfaces have been characterised by FESEM and AFM and demonstrate the resolution of our molding method. The bactericidal activity of both the moulds and Si master has been studied using static cultivation tests against Pseudomonas fluorescens.

Authors : Esti Toledo, Guillaume Le Saux, Angel Porgador, Mark Schvartzman
Affiliations : Avishai Edri, Uzi Hadad,

Resume : Innate immune system is based on natural killer (NK) cells, whose immune activity is regulated through a delicate balance among signals delivered by a multitude of activating and inhibitory receptors. However, the exact mechanism of how different receptors integrate their signals, and in particular how their signal integration depends on the receptor spatial organization, is unclear. Recently, biomimetic devices that control spatial organization of receptors within the cell membrane have been extensively used to study how the receptor spatial order regulates cell function, including that of immune lymphocytes. Yet, these devices have been limited to control only receptor of one type, and thus could not been used to study signal integration between different receptors. Here, we realized two types of biomimetic devices for the spatial control of inhibitory and activating receptors, whose signal integration is currently a subject of intensive study. The first type is based on photolithographically patterned lines of Ti and Au, orthogonally functionalized with activating and inhibitory ligands. Such devices spatially determine the micro-clustering of both receptors within the cells. The second type of devices is based on pairs of sub-10 nanodots of Au and Ti fabricated by nanoimprint lithography and selectively functionalized different ligands. Besides the used nanofabrication and functionalization approaches, we will present preliminary results of the study of NK cell immune response to various arrangements of ligands. This work provides a unique toolbox for the spatial control of diverse receptors within the cell membrane, that paves the way to numerous studies aimed at elucidating the molecular mechanism of signal integrating in cells, with the complexity and resolution impossible up to date.

Authors : Marta d?Amora1, Freddy Liendo2, Fabio A. Deorsola2, Samir Bensaid2, Silvia Giordani3
Affiliations : 1 CSF@PoliTo Torino, Istituto Italiano di Tecnologia, Via Livorno 60, 10144, Turin, Italy 2 Department of Applied Science and Technology, Politecnico di Torino, Corso Duca degli Abruzzi 24, 10129, Torino, Italy 3 School of Chemical Sciences, Dublin City University, Dublin, Ireland

Resume : Calcium carbonate nanoparticles (CaCO3NPs) derived from CO2 are currently being investigated as potential materials to be employed in different industrial applications, with the purpose of contributing to CO2 capture and utilization directly in the industrial site in which CO2 is available or produced. In this regard, the cement industry is one of the major contributors to anthropogenic CO2 emissions; therefore, the possibility to incorporate a CO2-derived filler in the cement matrix is very attractive [1]. Calcium carbonate nanoparticles are believed to increase the strength of the cement, thanks to their unique properties, including high surface area to volume ratio and high porosity. On the other hand, the increased human and environmental exposures to NPs gives rise to an urgent need for complete toxicological evaluations in biological systems. In this study we synthesized CaCO3 NPs from a CaO slurry, pumped into a packed bed reactor, where it gets in contact with the CO2. Here, the precipitation of the CaCO3 takes place, and then the resulting product is filtered and dried. The obtained product was thoroughly analyzed by focusing our attention on a careful in vitro and in vivo toxicity assessment of CaCO3NPs. The cell viability, reactive oxygen species (ROS) production and DNA damage are evaluated with different assays on two cell lines exposed to CaCO3NPs. These include normal mouse embryonic fibroblast cells as well as tumor cells of the breast. Moreover, the toxicity behavior of these nanoparticles is investigated on zebrafish (Danio Rerio) during the development [2] [3]. As the use of CaCO3NPs constantly increases, the correlation between our zebrafish toxicity and cellular tests will open new perspectives on the toxicological behavior and biosafety of this nanomaterial. References [1] J. Rieger, M. Kellermeier, L. Nicoleau, Angewandte Chemie, 2014, 53(46), 12380. [2] M. d?Amora, S. Giordani, Frontiers in Neuroscience, 2018, 12, 976. [3] M. d?Amora, A. Camisasca, S. Lettieri, S. Giordani, Nanomaterials, 2017, 7(12), 414. European Union?s Horizon 2020 (Recode Project) is greatly acknowledged for funding.

Authors : Sheng-Ying Cheng, Yu-Lun Chiang, Yu-Jui Chang, Shiao-Wen Tsai
Affiliations : Graduate Institute of Biomedical Engineering, Chang Gung University, Taiwan.

Resume : Introduction: One of the primary role to determine the overall success of the medical device is biocompatibility. In general, the type of material, surface properties, and bulk chemical and physical properties of materials are essential factors to determine the biological responses to the chosen materials. However, cells or proteins interaction with materials starting from surfaces, therefore, surface properties include roughness, wettability, and functionalization, are the key parameter on biological responses to a material. There are numerous of surface modification techniques have been developed to treat all types of biomaterials to satisfy specific requirements for a unique biomedical application. Nevertheless, based on intrinsic characteristic of bulk materials, there are few methods could simultaneously apply to an organic/inorganic hybrid. Herein, prebiotic-chemistry inspired coatings have been used to modify the composite surface. Methods: In this work, a layer of hydrogen cyanide (HCN)-derived polymers used to surface treated of mesoporous bioglass (MBG) nanoparticles/polycaprolactone (PCL) composites. Contact angle was used to measure the hydrophobicity. X-ray diffraction analysis (XRD) was used to determine the crystallographic structure of apatite. Alkaline phosphatase (ALP) activity assay was used to determine the differentiation level of cells. Results and Discussion: The final modified membranes show good stability in a buffer solvent for three weeks, and enhance hydroxyapatite formation compared with non-treated ones. An increasing number of osteoblast-like cells adhere on membrane and show a higher differentiation level when polymer coating was used as external surface. The results demonstrated that this modification method provides a facile and efficient strategy for the treatment of organic/inorganic composites.

Authors : Arindam Banerjee, Somenath Ganguly
Affiliations : Indian Institute of Technology Kharagpur, INDIA

Resume : Hydrogels prepared from natural polymers have received immense considerations over the past decade due to their safe nature, biocompatibility, hydrophilic properties, and biodegradable nature. Biomaterials made of hydrogels were developed for tissue regeneration, wound healing and drug delivery purposes. In this research, natural polymers namely alginate and gelatin were considered as the gel matrix. Voids were introduced in the form of monodisperse bubbles in submillimeter size into the aqueous suspension, prior to gelation. Alginate and gelatine was blended in aqueous suspension, followed by bubbling through fluidic device and crosslinking of alginate using CaCl2. Voids of 500µm diameter were embedded in monolayer or in multiple layers in the gel films. The benefits are the excellent absorption capacity of alginate, the mechanical strength of gelatin in one embodiment. Vitamin B12 was chosen for uptake and release studies. The mechanical strength was measured for stress-strain analysis in Universal Testing Machine under tensile and compressive loadings. The viscoelasticity of the gel matrix was characterized from stress relaxation measurement. The transient responses were studied through numerical simulation in ANSYS.

Authors : Martin Järvekülg1, Rasmus Liira1, Kaidi Möll2, Paula Reemann3, Mart Loog2 and Viljar Jaks4
Affiliations : 1. University of Tartu, Institute of Physics, W. Ostwaldi Str 1, 50411, Tartu, Estonia; 2. Institute of Technology, University of Tartu, Nooruse 1, 50411, Tartu, Estonia; 3. Institute of Biomedicine and Translational Medicine, University of Tartu, Ravila 19, 50411 Tartu, Estonia; 4. Institute of Molecular and Cell Biology, University of Tartu, Riia 23, 23b-134, 51010, Tartu, Estonia.

Resume : Gelatin can present chemical composition and biochemical properties that are well suited for designing artificial extracellular matrices. Glucose can be added to achieve additional crosslinking during thermal treatment to obtain a biocompatible material that preserves its nanoscale morphology in wet state. Recent studies demonstrate that the 3D surroundings its local mechanical properties also play a critical part in directing cell decisions. In tissue engineering usually three-dimensional scaffolds are required that could be populated by cells in all its volume. Therefore, various foam-like materials have been developed with large pore size and total pore volumes sufficient to allow cell migration throughout the material. However, these methods usually rely on bubbling or sacrificial templates, thus fail to mimic the fibrous nature of natural extracellular matrix. The aim of our work has been the development of three-dimensional microstructures of cross-linked gelatin. We present gelatin preforms and tissue constructs obtained by deposition from short elecrospun fibers, air- spinning of felts (see figure) and immersion precipitation. As the mechanical properties as well as degradation/resorption rate of crosslinked/stabilized gelatin can also be easily tuned, the combination of applied approaches presents a superior platform for three-dimensionally functional resorbable scaffolds.

Authors : Adithya Vivek, 1st Supervisor: Dr. Yuval Elani, 2nd Supervisor: Dr. Nick Brooks
Affiliations : Membrane Biophysics Group; Dept. Chemistry -Imperial College London

Resume : Bottom-up approaches in synthetic biology have led to a small variety of design motifs for artificial cells, most simple, bilayer-centric constructions of lipid constituency modification. We have produced the first-of-its-kind “cellular exoskeleton”, instilling novel mechanical properties in cell mimics by designing co-membranous, rigid structures whilst maintaining good vesicle integrity. This is a realization in soft-hard matter hybridization. Model cells are giant unilamellar vesicles (GUVs) of ternary lipid mixture closely imitating biological cells’ dynamics. The composition creates two-phase fluid coexistence. Vesicle populations are introduced to gold(Au) nanospheres at stable 150nm sizings, preventing nanopore formation. Induced disturbance in the dual-phase culminate in extensive, rigid branch networks with free mobility in the liquid-disordered (LD) background, interstitial with bilayer, assuming ~25% GUV surface area. A range of operations are performed on the exoskeletons with optical tweezers, enabling 2D manipulation & cell-cell fusions. Observations are chiefly via fluorescence microscopy. DSC energetic & AFM mechanical characterizations are undertaken. Image analysis for bulk dynamics can define phase behaviours in relation to active events. Viabilities as drug delivery systems (DDS) or as original platforms for modular, soft micromachines are foreseeable. Integration of gold, a strong inorganic conductor, is further interesting for nanoelectronics insights.

Authors : Michal M. Godlewski, Paula Kielbik, Anna Slonska-Zielonka, Waldemar Lipinski, Jaroslaw Olszewski, Mikolaj A. Gralak, Zdzislaw Gajewski, Jaroslaw Kaszewski, Rafal Pietruszka, Bartlomiej S. Witkowski, Marek Godlewski
Affiliations : Michal M. Godlewski, Paula Kielbik, Anna Slonska-Zielonka, Waldemar Lipinski, Jaroslaw Olszewski, Mikolaj A. Gralak, Zdzislaw Gajewski: Faculty of Veterinary Medicine, Warsaw University of Life Sciences ? SGGW, Nowoursynowska St, 02-776 Warsaw, Poland; Jaroslaw Kaszewski, Rafal Pietruszka, Bartlomiej S. Witkowski, Marek Godlewski: Institute of Physics, Polish Academy of Sciences, Al. Lotnikow 32/46, 02-668 Warsaw, Poland

Resume : Currently, cancer-related deaths may for the first time in history become the major cause of death in the developed countries. Furthermore, current diagnostic and therapeutic strategies are inadequate, as they are commonly failing to detect and eradicate small tumours and metastases. Exponentially growing field for research in the nanomaterials prompts an enormous potential of possible applications of nanoparticles (NPs) in medicine. We focused on the applications of biocompatible, high-k oxide, nanoparticles in the field of cancer diagnosis and therapy. This work was focused on the potential development of multimodal detection-therapeutic system with dopant-dependent contrasting properties in the magnetic and fluorescent resonance, coupled with the ability to traffic drugs directly to the tumour site. All experimental protocols were according to EU guidelines and approved by LEC. Mice received suspension of hydrothermally created NPs (10 mg/ml, 0.3 ml/mouse). Following oral administration, NPs were passively targeted to all tumour tissues by enhanced permeation and retention (EPR) effect. In the lungs NPs were targeted specifically to the areas of metastases making them a highly specific diagnostic tool for cancer in this tissue. Furthermore, bioactive compounds linked to the NPs were transported through the blood organ barriers and deposited in the tissues. Research supported by: KNOW:05-1/KNOW2/2015, NSC: DEC-2012/05/E/NZ4/02994 and DEC-2012/0139/N/ST3/04189.

Authors : Jae-Young Jeong, Yong-Hoon Jeong, Jae-Woong Yang, Kwang-Min Park, Kwan-Su Kang, Ji-Sun Park, Tae-Gon Jung
Affiliations : Department of R&D, OSONG Medical Innovation Foundation

Resume : To improve the chemical stability and modify the bio-mechanical characterization of bio-ceramic materials, their correlation should essentially verify with finding synthetic parameters to be suitable for clinical application. The object of this study is to investigate the effects of heat treatment temperature condition on bio-ceramic materials for improvement of mechanical properties of bio-ceramic scaffold. Bio-ceramic scaffolds of the composition (% wt., 53SiO2-23CaO-22Na2CO3-2P2O5) was prepared by mixing with chemical binder. Scaffold structure was fabricated by three dimensional deposition method, and sintering conditions were applied three different sintering temperature (900, 950, and 1000℃) and, while the temperature elevation with 1, 3, and 5 ℃/min until 900 ℃ in furnace. The material characteristics were investigated with field emission scanning electron microscope (FE-SEM), X-ray diffraction (XRD), and nano-indentation test to analyze surface morphology, phase structure, hardness, and elastic modulus, respectively. The hardness was shown similar with three sintering temperature, however, elastic modulus was increased with decreasing temperature. Micro-structural observations were shown the surrounded crystalline clusters by glassy matrix and asymmetrical shapes. The crystal structure was transformed from silicon dioxide (SiO2) to sodium calcium silicate (Na6Ca3Si6O18) while the hardness and elastic modulus was increased with decreasing temperature increment rate.

Authors : B.Di Napoli, M.G.L.Messina, C.Mazzuca, E.Gatto, M.De Zotti, F.Formaggio, A.Palleschi, G.Marletta
Affiliations : B.Di Napoli, C.Mazzuca, E.Gatto, A.Palleschi: Department of Chemical Science and Technology, University of Rome Tor Vergata, Via della Ricerca Scientifica, 00133 Roma, Italy; M.G.L.Messina, G.Marletta: Laboratory for Molecular Surfaces and Nanotechnology, Department of Chemical Sciences, University of Catania and CSGI, Viale Andrea Doria 6, 95125, Catania, Italy; M.De Zotti, F.Formaggio: CB Padova Unit, CNR, Department of Chemistry, University of Padova, 35131 Padova, Italy

Resume : In the framework of a fully characterization on the formation of peptidic monolayer on solid surfaces, the difference in behaviour of two chemisorbed peptide, a monomeric (L1) and the corresponding dimeric (L2) Trichogin GA IV analogs are performed. Trichogin GA IV has the following sequence: Oct-UGLUGGLUGI-Lol, while in the L1 and L2 analogs all the glycine residues have been substituted by lysine residues (to obtain stimuli responsive peptides) and in both there is a lipoic group at N-terminus replacing the octanoyl group, for binding the gold surface. To exploit the protonation/deprotonation equilibria, pH was switched from acid to basic condition. Experiments and MD simulations indicate that the differences in peptide density on surface with pH are enhanced in the case of L2, in which the water amount inside the peptide layer is higher (not double) at pH=3 than L1. Thus, the effect of pH cycling is a complex response of tightly interconnected molecular systems involving changes in the mechanical properties of the peptide layers.

Authors : W. Kajzer, J. Szewczenko, A. Kajzer, M. Basiaga, M. Kaczmarek, M. Antonowicz, J. Jaworska, K. Jelonek, J. Kasperczyk
Affiliations : W. Kajzer; J. Szewczenko; A. Kajzer; M. Basiaga; M. Kaczmarek; M. Antonowicz - Silesian University of Technology, Faculty of Biomedical Engineering, Department of Biomaterials and Medical Devices Engineering, Roosevelta 40, 41-800 Zabrze, Poland. J. Jaworska; K. Jelonek; J. Kasperczyk - Centre of Polymer and Carbon Materials, Polish Academy of Science, M. Curie-Sklodowska 34, 41-819 Zabrze, Poland.

Resume : The aim of the work was to determine the influence of biodegradable polymer coatings on the corrosion resistance of the anodized Ti6Al7Nb alloy. Biodegradable coatings made of poly(glycolide-caprolactone)-G-Cap and poly(glycolide ?-caprolactone-lactide)-G-Cap-L were applied in the test. The reference was a coating made of poly (lactide-glycolide)-PLGA. The coatings applied by dip-coating after one, two and three dips were analyzed. Corrosion resistance was assessed on the basis of potentiodynamic studies. The studies were carried out on samples after 30, 60 and 90 days of exposure to Ringer's solution. The degradation process of the base material was evaluated on the basis of the mass density of metal ions released to the solution. In addition, the samples were observed both before and after exposure to Ringer's solution. The analysis of the test results indicates the influence of the coating type on corrosion resistance. In addition, a beneficial effect of the polymer coating was found, irrespective of its application parameters, on the reduction of the density of the released metal ions with respect to the samples not coated with the polymer coatings. This dependence was observed after all exposure periods. The obtained results provide the basis for the development of polymer coatings enriched with active substances characterized by specific degradation that do not reduce the corrosion resistance of metal substrate. Acknowledgements. The work is the result of the research project No. 2015/19/B/ST5/03431 funded by the National Science Centre.

Authors : Raj Kumar and Orit Shefi
Affiliations : Bar Ilan Institute of Nanotechnology and Advanced Materials and Faculty of Engineering, Bar Ilan University, Ramat Gan-5290002, Israel

Resume : There is a growing need for biocompatible nanocomposites that may efficiently interact with biological tissues through multiple modalities. Carbon dots (CDs) could serve as biocompatible fluorescence nanomaterials for targeted tissue/cell imaging. Important goals toward this end are to enhance the fluorescence quantum yields of the CDs and to increase their targetability to cells. we synthesized carbon dots doped with different metals (Au, Ag, Ga, Zn and Sn) and elements (B, N and P) synthesized using acoustic cavitation and hydrothermal methods respectively. Thoroughly investigated the effect of different experimental parameters on physico-chemical properties. Size and shape were studied using transmission election microscope imaging. particle size ranges from 2-10 nm. Prepared carbon dots showed good quantum yield. The prepared carbon dots interactions with neural cells was investigated and showed minimum cytotoxicity and good cellular uptake. Moreover, the influence of the doping into carbon dots on the improvement of neurites during initiation and elongation growth phases were compared with pristine carbon dots. Our research demonstrates the use of carbon dots for imaging and for neuronal interactions. The prepared carbon dots are promising due to their biocompatibility, photo-stability and potential selective affinity, paving the way for multifunctional biomedical applications.

Authors : P. Gkertsiou, Z. Dardani, S. Kassavetis, A. K. Tsiapla, V. Mpakola, C. Kamaraki, C. Gravalidis, V. Karagkiozaki, S. Logothetidis
Affiliations : Nanotechnology Lab LTFN, Aristotle University of Thessaloniki, 54124, Thessaloniki, Greece

Resume : By virtue of its physical properties, biodegradability and low cost, polycaprolactone (PCL) is gaining popularity as a polymeric material for nanofibers and scaffolds development, with various applications such as drug delivery, tissue engineering and antimicrobial surfaces. Mechanical stresses to which the scaffolds are subjected, cell signalling and their development make evident that the study of their mechanical properties is critical. In this study, PCL nanofibers scaffolds with embedded drugs (Curcumin, Vancomycin) and ZnO nanoparticles (NPs) were manufactured. The effect of drugs and ZnO NPs on the mechanical properties of individual PCL fibers, was tested thoroughly by Nanoindentation Continuous Stiffness Measurement (NI) technique using a Berkovich type diamond nanoindenter to deform the fibers and to study their resistance to point/axial loading. The NI testing showed that the addition of Curcumin, Vancomycin drugs did not significantly alter the mechanical properties (Hardness (H) and Elastic Modulus (E)) of the fibers in contrast to ZnO NPs. In that case the E increases from 1.2 GPa (neat PCL fibers) to 1.7 GPa, whereas the H is almost the same. Furthermore, the Atomic Force Microscopy (AFM) probe was used: a) to deform the fibers and to estimate the critical load for the onset of the fibers elastic/plastic deformation and the formation of a clear imprint on the fibers surface and b) to test the adhesion of ZnO(NPs):PCL fibers to the substrate. The AFM force lithography showed that although the ZnO(NPs):PCL fibers are subjected to plastic deformation and cutting, they remained adhered on the substrate.

Authors : Lungu I.1,2, Badoi A.1, Gavrila Florescu L.1, Dumitrache F.1, Fleaca C.1, Staicu A.1, Ilie A.1, Banici AM.1, Greculeasa S.3, Vasile E.4
Affiliations : 1. National Institute for Lasers, Plasma and Radiation Physics, 409 Atomistilor Str., PO Box MG-36, Magurele, Ilfov, Romania 2. Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest 3. Natl Inst Mat Phys, POB MG-7, Magurele 77125, Romania 4. Politehnica” University of Bucharest, Faculty of Applied Chemistry and Materials Sciences, 1-7 Gh. Polizu Str., Bucharest, Romania

Resume : In this paper we use several types of magnetic nanoparticles synthetisized by laser pyroysis in our own laboratory; such as iron oxide – based nanoparticles doped or not with nitrogen, core-shell type nanoparticles containing a iron oxide core and a carbon shell, as well as silica coated iron oxide nanoparticles. Investigations on the magnetization of these nanoparticles (NPs) showed that these iron oxide-based nanoparticles exhibit higher magnetic results than other types. The NPs have been stabilised using carboxymethyl cellulose (CMCNa), L-3,4-dihydroxyphenylalanine (L-Dopa) and Chitosan; the solution were obtained at different concentrations of both NPs and stabilizers. Due to its impressive properties and organic nature, Protoporphyrin IX was chosen for further functionalization of the system. In order to obtain a complete set of results, for comparison purposes, the functionalization was completed in both basic and acid pH, aqueous medium, as well as PBS. X-ray Diffraction (XRD), Energy-dispersive X-ray spectroscopy (EDX), Magnetization analysis, Transmission electron microscopy (TEM) were used to characterize the resultes.

Authors : Francisca Gomes 1, Inês Cruz 1, Paula Parreira 2, Mariana Rocha 2, Clara Pereira 3, Cristina Martins 2, André M. Pereira 1
Affiliations : 1 IFIMUP, Department of Physics and Astronomy, Faculty of Sciences, University of Porto, Porto, Portugal; 2 i3S?Instituto de Investigação e Inovação em Saúde, Universidade do Porto, Portugal; 3 REQUIMTE/LAQV, Department of Chemistry and Biochemistry, Faculty of Sciences, University of Porto, Porto, Portugal;

Resume : Biomaterials have been applied in several areas of science and medicine, namely orthopaedics, tissue engineering, biosensors and drug delivery. Although exhibiting promising results, these versatile biomaterials are still in a growing process, especially those combining more than one functionality. This is even more remarkable with the advent of bionanomaterials, where the emergence of new effects is a reality, promoting in this way a new branch that has evolved since the beginning of the century. Magnetic nanoparticles (MNPs) and chitosan are two well used materials in several approaches, from removal of toxic metal and dyes from aqueous solutions to drug delivery and medical diagnostics. Typically, the preparation of these multifunctional materials is a two-step procedure involving the synthesis of MNPs, followed by a chitosan coating through chemical methods to form core-shell systems. However, and most importantly, works describing the one-pot preparation of these multifunctional biomaterials are still scarce. The present work is focused on the preparation of core-shell magnetic chitosan microspheres through a one-pot method, wherein the synthesis of spinel ferrite was performed during chitosan purification. The aforementioned core-shell particles were characterized in terms of particle size and morphology by SEM, degree of crystallinity and phase composition by XRD, and magnetic behavior by SQUID, with ZFC-FC and isothermal magnetization curves.

Authors : Bogdan, I.M.(1), Tite, T.(1), Balescu, L.M.(1), Iconaru, S. (1), Ciobanu, C.S. (1), Predoi, D. (1), Popa, A.C.(1,2), L. Albulescu (3), C. Tanase (3), S. Nita (4), Stan, G.E.(1)
Affiliations : (1)National Institute of Materials Physics, RO-077125 Magurele, Romania (2)Army Centre for Medical Research, RO-010195 Bucharest, Romania (3)“Victor Babes” National Institute of Pathology, Bucharest 050096, Romania (4) National Institute for Chemical Pharmaceutical Research and Development, Bucharest, Romania

Resume : The use of hydroxyapatite (HA) in biomedicine, a synthetic biomaterial promoting new bone formation, is often limited due to its slow osteointegration rate and absent antibacterial activity. Recent findings in the realm of ion-substituted HA could be an important step to pave the road towards significant developments in orthopedic and dentistry, with an emphasis on a new generation of biointerface. This work show the synthesis, detailed characterization and biological performance of zinc (Zn:HA) and magnesium (Mg:HA) single substituted HA as promising bioceramics. Zn:HA and Mg:HA powders for molar concentration in the range 0.0055 mol% and xZn>x mol%).

Authors : Bogdan, I.M.(1), Tite, T.(1), Balescu, L.M.(1), Popa, A.C.(1,2), L. Albulescu (3), C. Tanase (3), S. Nita (4), Stan, G.E.(1)
Affiliations : (1)National Institute of Materials Physics, RO-077125 Magurele, Romania (2)Army Centre for Medical Research, RO-010195 Bucharest, Romania (3)“Victor Babes” National Institute of Pathology, Bucharest 050096, Romania (4) National Institute for Chemical Pharmaceutical Research and Development, Bucharest, Romania

Resume : The increasing application of biomaterials based on synthetic hydroxyapatites (HA) as bone substitutes imposes the preparation of ion substituted HA with a composition which imitates that of the mineral phase of natural bone. This work describe the synthesis, detailed characterization and biological performance of strontium (Sr:HA) and cerium (Ce:HA) single substituted HA as alternative biomaterials to HA which has a low antibacterial activity and slow osteointegration rate. Sr:HA and Ce:HA powders at low molar concentration (0.005<{xSr, xCe}<0.025) were synthesized by co-precipitation method and thermal treated at 500ºC. The morphology, chemistry, composition, structure, and biocompatibility of the samples were investigated by SEM, XPS, EDXS, XRD, and FTIR-ATR measurements and biological in vitro assays (degradation, ion release, cytocompatibility, osteogenesis, ROS reduction). The successful substitution of Sr2 and Ce ions, present in the samples as mixed Ce3 and Ce4 valence oxidation states, has been demonstrated. XRD and FTIR analyses confirmed Sr:HA and Ce:HA monophasic hexagonal HA phase. Interestingly, biological tests indicate that the Sr and Ce doped HAs possess promising biological performance (good cytocompatibility, controlled release of therapeutic ions, etc). Our findings could open new gateway towards smart biomedical interfaces for application in orthopedic and dentistry.

Authors : Xiaoqiu Dou[a,b], Chuanliang Feng[a], and Holger Schönherr[b]*
Affiliations : [a] Xiaoqiu Dou, Chuanliang Feng: State Key Lab of Metal Matrix Composites, School of Materials Science and Engineering, Shanghai Jiaotong University, Dongchuan Road 800, 200240, Shanghai, China [b] Xiaoqiu Dou, Holger Schönherr: Physical Chemistry I and Research Center of Micro and Nanochemistry and Engineering (Cμ), Department of Chemistry and Biology, University of Siegen, Adolf-Reichwein-Str. 2, 57076, Siegen, Germany.

Resume : Rose petal derived structured and epithelial cell adhesion molecule antibody (anti-EpCAM) functionalized polydimethylsiloxane (PDMS) substrates were fabricated as new three-dimensional hierarchical surfaces for efficient capture of circulating tumor cells (CTCs). Compared to flat PDMS without any surface structures, these hierarchical substrates exhibited higher capture ability. As indicated by the scanning electron microscope (SEM) and immunofluorescent images, this enhancement can be partly attributed to the interaction between nanoscale cell surface components and nanostructures on substrate (topographical interaction). From other side, PDMS with hierarchical structures leads to increased surface area, allowing more anti-EpCAM to be immobilized on the surface, which increases the number of available sites on the surface for cell adhesion. Furthermore, treating the substrates with biocompatible reductant glutathione (GSH), 79%-85% of the captured cells can be released with the disulfide bonds being cleaved. The live/dead cell staining confirmed that the released cells display over 98% cell viability after release. Therefore, this bio-inspired hierarchical structured and functionalized substrates can be successfully applied to capture CTCs, as well as release CTCs for subsequent analysis, providing new prospects for designing cell-material interfaces for advanced cell-based biomedical studies in the future.

Authors : Andreas Schielke, Lisa Gamrad, Carmen Streich, Christoph Rehbock, Stephan Barcikowski
Affiliations : Technical Chemistry 1 and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen; Technical Chemistry 1 and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen; Technical Chemistry 1 and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen; Technical Chemistry 1 and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen; Technical Chemistry 1 and Center for Nanointegration Duisburg-Essen (CENIDE), University of Duisburg-Essen

Resume : Laser-generated, ligand-free gold nanoparticles can be easily conjugated with functional ligands via thiol-gold chemistry yielding conjugates with exceptionally high surface coverage and precise control of ligand/nanoparticle ratios. In case ligand charge and surface coverage are precisely balanced, a successful functionalization can be achieved, allowing the utilization of the respective conjugates as either biosensors, molecular transport units or therapeutic platforms. In this work selected applications of laser-fabricated nano-bio-conjugates (NBC) featuring cationic ligands are highlighted. For once, monodisperse gold NBCs may serve as a platform for functional peptide ligands, aiming at the termination of Aβ-protein aggregates, which have been linked to neurodegenerative diseases. Multiple biophysical assays indicate that ligands decorated on a NP surface were even superior to the free ligands in dissolving Aβ fibrils. In a second example, deliberately agglomerated NBCs could be established as photo-induced intracellular release systems, which could deliver fluorescent cargo molecules (dyes) into the cytoplasm of model cell lines. Finally, cationic peptides can also be combined with aptamers to produce multifunctional NBCs with variable surface coverage suitable for in vitro diagnostic purposes. All these approaches could provide novel strategies in biomedicine with respect to diagnostics, molecular transport, and therapeutics.

Authors : Sung Bum Park1, SeungHyun Park2, Md Shahjahan Kabir Chowdury1, Won Hyung Ryu2, Yong-il Park1
Affiliations : 1 Department of Advanced Material Science and Engineering, Kumoh National Institute of Technology, 61 Daehak-ro, Gumi, Gyeongbuk, 39177, Korea; 2 School of Mechanical Engineering, Yonsei University, 262 Seongsanno, Seodaemun-gu, Seoul 120-749, Korea

Resume : Recently, there have been increasing interests in mesoporous silica especially in the field of controlled drug delivery. It is increasingly important to control the degree of bioactivity and rate of biodegradation of such mesoporous silica. In this study, manufactured the microporous(2nm~50nm) silica Nanorods by perfectly filling the TEOS solution using the pumping system in porous anodic alumina oxide(AAO)-the porous scaffold-with the most widely used metal alkoxide, Tetraethylorthosilicate(TEOS-si based), and their drug-delivery performance were investigated. In addition, in order to use in intraocular drug delivery system, paramagnetic mesoporous nanoparticles having SPION (superparamagnetic iron oxide nanoparticle) cores were also fabricated by coating SPION nanoparticles with the same silica precursor sol which was used for the fabrication of the mesoporous silica nanorods. SPIONs can achieve the highest drug targeting efficiency, an external magnetic field locally applied to the target. The porosity and biodegradation kinetics of the fabricated mesoporous nanorods and magnetic nanoparticles were analyzed using SEM, TEM, XRD, FTIR. The performance of the mesoporous silica nanorods as drug delivery carrier and intraocular drug delivery efficiency of the fabricated magnetic nanoparticles were evaluated.

Authors : Ioritz Sorzabal Bellido, Yuri A. Diaz Fernandez, Arturo Susarrey-Arce, Adam Skelton, Fiona McBride, Alison J. Beckett, Ian A. Prior, and Rasmita Raval
Affiliations : Dr. I. Sorzabal Bellido; Dr. Y.A. Diaz-Fernandez; Dr. A. Susarrey-Arce; Dr. F. McBride; Prof. R. Raval Open Innovation Hub for Antimicrobial Surfaces, University of Liverpool, L69 3BX, UK Dr. A. J. Beckett; Prof. I, A. Prior, Biomedical EM Unit, University of Liverpool, L69 3BX, UK Dr. Adam Skelton Department of Chemistry, University of Liverpool, L69 3BX, UK

Resume : Colonisation and biofilm formation on medical devices is driving an urgent need for novel antibacterial strategies. Smart antibacterial surfaces are a powerful tool to prevent the initial bacterial colonisation that eventually leads to medical device failure. In this work, we report the surface functionalisation of polydimethylsiloxane (PDMS) materials, widely used in medical devices, with salicylic acid (SA), a biocide approved for use in humans. Good surface location and release properties were obtained via two-step functionalisation with APTES and IPTES silane anchoring moieties, which play a key role in delivering antimicrobial properties. Cell viability assays on planktonic and sessile bacteria and SEM characterisation of bacterial attachment were carried out for three model microorganisms associated to medical device biofilms, E. coli, S. aureus and S. epidermidis, showing that silane functionalisation enhanced the action of salicylic acid on preventing bacterial colonisation. XPS, ATR-FTIR and Raman characterisation revealed that surface activity is closely related to the properties embedded at the surfaces. We demonstrated that our surface modification approach led to effective antibacterial coatings based on surface-located interactions that allow the creation of stacking nucleation points of the biocide at the interface. This approach could be translated to existing medical devices and be used to prevent surface colonisation by bacterial pathogens.

Authors : Gabriela Ciobanu, Maria Harja
Affiliations : ”Gheorghe Asachi” Technical University of Iasi, Faculty of Chemical Engineering and Environmental Protection, Iasi, Romania

Resume : This study makes evident the possibility of the Bi-doped hydroxyapatite nanocrystals to be deposited on the titanium implant surface by a solution-derived process according to an established biomimetic methodology. In order to increase the bioactivity of the titanium surface an alkali ÷ thermal oxidation treatment has been applied. Titanium implants were then coated with a Bi-doped hydroxyapatite layer under biomimetic conditions by using a supersaturated calcification solution (SCS) modified by adding a bismuth salt. The apatite deposits were investigated by means of scanning electron microscopy coupled with X-ray analysis (SEM-EDX), X-ray photoelectron spectroscopy (XPS), X-ray diffraction (XRD) and digital X-rays radiography method. The obtained results confirmed that the nanohydroxyapatite coatings on titanium surface were produced and bismuth ions incorporated into hydroxyapatite lattice. The Bi-doped hydroxyapatite coatings exhibit radiopacity, enhancing thus their applications in dental and orthopedic fields. These coatings show antimicrobial activity against Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus bacteria.

Authors : Tzu-Yi Yu, Ta-Ching Chen, Wei-Fang Su
Affiliations : Department of Materials Science and Engineering, National Taiwan University, Taipei, Taiwan

Resume : Hydrogels and porous scaffolds are two major categories of biomaterials used in tissue engineering. These two materials exhibit different, but complementary properties. Hydrogels are easy to fabricate and injectable in clinic but they are soft and lack of mechanical integrate for cell attachment and directed cell growth. On the other hand, porous scaffolds can be fabricated by electrospinning with aligned 3D fibrous structure that promotes cell migration and directional growth. However, the scaffold needs surgically implanted into human body. To take the merits of each material, one can make injectable nano-composite hydrogels with mechanical integrate for clinic use. So far, most nano-composite hydrogels used in tissue engineering are composed of peptide self-assembly nano-particles which are crosslinked by divalence ions. By ionic crosslinking, the nano-composite hydrogels are soft enough for injection and nano-particles become 2D sheet to adhere cells at the same time. To be able to self-assemble into nano-particles, these peptides have to have specific amino-acid sequence, which is high-cost, time-consuming and low yield in synthesis. Thus, we develop a new kind injectable nano-composite hydrogel basis on polypeptide and cellulose nano-fiber (CNF). The polypeptide is synthesized using conventional ring opening polymerization of r-benzyl-L-glutamate N-carboxy anhydride. A portion of side chains of poly (r -benzyl-L-glutamate) is modified by -NH3+Cl- terminated ethylene glycol. This modification make the polypeptide become water-soluble. The synthesized polymer is characterized by GPC, NMR and IR to confirm its molecular weight and chemical structure. The nanocomposite is made by blending modified polypeptide with CNF. The modified side chain is capable to interact with CNF to form hydrogen bond that results in hydrogel. Furthermore, the material has 3D structure with directional frame work that has potential application in the required directional growth of neural tissue engineering.

Authors : I. Negut1, R. Cristescu1, C. Popescu1, A. Visan1, G. Dorcioman1, A. Popescu1, D. Istrati2, D.E. Mihaiescu2, M. Popa3, M.C. Chifiriuc3, R.J. Narayan4, D.B. Chrisey5
Affiliations : 1 National Institute for Lasers, Plasma & Radiation Physics, Bucharest-Magurele, Romania 2 Faculty of Applied Chemistry and Materials Science, Politehnica University of Bucharest, Bucharest, Romania 3 Microbiology Immunology Department, Faculty of Biology, Research Institute of the University of Bucharest - ICUB, Bucharest, Romania 4 Department of Biomedical Engineering, University of North Carolina, Chapel Hill, NC, USA 5 Department of Physics and Engineering Physics, Tulane University, New Orleans, LA, USA

Resume : Antimicrobial peptides (AMPs) are promising alternatives to antibiotics for the treatment of drug-resistant and biofilm-associated infections, which are a serious global health threat. Here, we report on the successful fabrication of bioactive composite nanocoatings, consisting of nanoencapsulated AMPs in mesoporous biopolymeric/magnetic nanoparticles, using the Matrix Assisted Pulsed Laser Evaporation (MAPLE) technique, for potential use in biofilm-prevention applications. Characterization of the nanocoatings included SEM, AFM, TEM, and XRD to understand coating uniformity, nanoparticle shape, and crystallinity; the chemical functional groups and bonding of the target (starting material) and coating were compared using FT-IR and HR-MS. Adhesion tests to assess the substrate-nanocoating interface were also performed. The antimicrobial activity was evaluated on ESKAPE ?antibiotic immune? microorganisms, in planktonic and biofilm growth state, using culture-dependent and quantitative methods. The biocompatibility of the obtained nanocoatings was investigated using in vitro models. The results of our studies reveal that the mesoporous biopolymeric/magnetic nanoparticle composite nanocoatings prepared by MAPLE are biocompatible and release the nanoencapsulated AMPs in active form. This approach may be employed to enhance the anti-biofilm properties of implants, medical devices, and other surfaces.

Authors : Popa, A.C.(1,2), Tite, T. (1), Bogdan, I.M. (1), Fernandes, H.R. (3), Necsulescu, M.(2), C. Luculescu, C.(4), Cioangher, M.(1), Dumitru, V.(1), Stuart, B.W.(5), Grant, D.M. (5), Ferreira, J.M.F.(3), Stan, G.E. (1)
Affiliations : (1)National Institute of Materials Physics, 077125 Magurele-Ilfov, Romania (2)Army Centre for Medical Research, 020012 Bucharest, Romania (3)Department of Materials and Ceramics Engineering, CICECO, University of Aveiro, 3810-193 Aveiro, Portugal (4)National Institute for Lasers, Plasma and Radiation Physics, 077125 Magurele-Ilfov, Romania (5)Advanced Materials Research Group, Faculty of Engineering, University of Nottingham, NG7 2RD, UK

Resume : The current research endeavors in the biomedical field are focused on innovative biointerface materials design that can replace the classical silica-based bioactive glass (SBG) systems, possessing a significant thermal expansion coefficient (CTE) mismatch with respect to Ti-based alloys, and simultaneously endow with superior biological functionalities (e.g. coupled antimicrobial effect and low cytotoxicity). In this context, alkali-free SBG with ZnO and/or SrO additives (in concentrations of 0?12 mol%) synthesized by melt-quenching are proposed in this work as alternatives. The SBGs powders were evaluated by XRD, FTIR, micro-Raman spectroscopy, dilatometry and ICP-MS. For biological evaluation, antibacterial (against Staphylococcus aureus and Escherichia coli strains) tests, and human mesenchymal stem cells cytocompatibility assays were also carried out. The results showed that the coupled incorporation of zinc and strontium ions into the parent glass composition has a synergetic benefit. In particular, the ?Z6S4? formulation (mol%: SiO2?38.49, CaO?32.07, P2O5?5.61, MgO?13.24, CaF2?0.59, ZnO?6.0, SrO?4.0) conferred strong antimicrobial activity against both types of strains, minimal cytotoxicity combined with good stem cells viability and proliferation, and a CTE (~8.7×10?6 ×°C?1) matching well those of the Ti-based implant materials. Our work opens new perspectives in the crucial development of future mechanically adherent implant-type SBG coatings.

Authors : O. Deschaume (1), J. Wellens (1), W. Yu (1), S. Jooken (1), P. Lettinga (1,2), W. Thielemans (3), C. Bartic (1)
Affiliations : (1) Soft Matter Physics and Biophysics unit, Department of Physics and Astronomy, KU Leuven, Celestijnenlaan 200D - box 2416, 3001 Leuven, Belgium,; (2) Forschungszentrum Jülich, Institute of Complex Systems (ICS-3), 52425 Jülich, Germany; (3) Renewable Materials and Nanotechnology Research Group, Department of Chemical Engineering, KU Leuven, Campus Kulak Kortrijk, Etienne Sabbelaan 53, 8500 Kortrijk, Belgium.

Resume : In living tissues, cells are supported by a 3D extracellular matrix (ECM) that controls and supports cellular functions. A plethora of nanomaterials have been engineered to mimic the properties of fibers present in natural ECMs. Moreover, nanomaterials can be combined to synthetic scaffolds to add wireless, localized cellular cueing properties. Among potential scaffold materials, cellulose nanocrystals (CNC) are attractive owing to cellulose availability, excellent mechanical properties and functionalization possibilities [1]. In this work, we construct 2D matrices based on CNC and in-situ grown gold nanoparticles (AuNPs) allowing for light-driven, photothermal and electrical cell stimulation. The effect of deposition parameters on scaffold properties is studied with atomic force microscopy and spectrophotometry. SH-SY5Y cells are grown on the CNC-AuNP surfaces and monitored by optical microscopy and metabolic assays. CNC patterning and coverage are controlled with micro-contact printing. As previously observed for other biological fibers [2], AuNPs selectively grow from CNC, their morphology being controlled from spherical to wire shape by varying growth conditions. Satisfactory cellular viability and positive preliminary cell actuation results show excellent prospects for localised cellular stimulation in both 2 and 3D using hybrid CNC scaffolds. [1] Eyley, S., Thielemans, W. Nanoscale 2014, 6, 7764-7779. [2] Deschaume, O. et al. Chem. Mater. 2014, 26, 5383–5393.

Authors : Viviana C.L. Caruso,1,2 Vanessa Sanfilippo,1,2 Lorena M. Cucci, 1,2 Valentina Greco,2 Giusy Villaggio,1,2 Cristina Satriano1,2
Affiliations : 1 Hybrid Nanobionterfaces Lab (NHIL), Department of Chemical Sciences, University of Catania, Italy; 2 Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (C.I.R.C.M.S.B.), Italy

Resume : Gold nanoparticles (AuNP) are ideal theranostic platforms, due to their unique optoelectronic and biological properties [1]. Hyaluronic acid (HA)-derived conjugates and nanoparticles that specifically binds the CD44 receptor, overexpressed in many cancer cells, have been reported for targeted delivery of therapeutics and imaging agents [2]. The HA biological activity, which depends on the molecular weight, is strongly affected in vivo by enzyme degradation as well as in extreme reaction conditions such as the high temperature[3]. In this work, AuNP coated with HA at low (200 kDa) and high (700 kDa) molecular weight were synthesized by chemical reduction at room temperature (25°C), using glucose as reducing/capping agent. The fluorescein-labelled HAF derivative was used as well. UV-visible, AFM and DLS were used to scrutinise the plasmonic features, the morphology and the hydrodynamic size of HA-AuNP. The interaction of HAF-AuNP with model cell membranes made of rhodamine-labelled supported lipid bilayers was characterised by FRET and QCM-D. Confocal cell imaging and viability tests performed on CD44 overexpressing (PC3 line) and non-expressing (SHSY5H line) cells demonstrated selective targeting and dose-dependent cytotoxicity. 1. P. Di Pietro et al., Curr Top Med Chem (2016) 16, 3069. 2. D. Bhattacharya et al., J Mater Chem B. (2017) 5, 8183 3. K.M. Lowry et al., J Biomed Mater Res (1994) 28, 1239

Authors : Seung-Hoon Um, Sang-Hoon Rhee
Affiliations : Department of Dental Biomaterials Science, School of Dentistry, Seoul National University

Resume : The effects of grain-boundary on the osteoconductivity of hydroxyapatite were newly investigated. The hydroxyapatite powder was synthesized by reacting a Ca(OH)2 suspension with an H3PO4 solution. The hydroxyapatite disks, which had small (specimen S) and large (specimen L) grain sizes, were prepared through microwave sintering at 1100 oC for 6 min and 720 min, respectively. The average grain size of specimen S was about 15 times smaller than that of specimen L. Their surface roughnesses were the same after polishing. The surface energy of specimen S, obtained from contact angle measurements, was about 1.6 times higher than that of specimen L. The adsorbed amounts of total serum proteins, fibronectin, vitronectin, and osteogenic growth peptide, substances related to osteogenic capacity, were all about two times higher on specimen S than on specimen L. The attachment and proliferation activities of pre-osteoblastic cells evaluated by MTS assay were also enhanced on specimen S as compared to specimen L. The differentiation capacity measured by alkaline phosphatase and Alizarin Red S activities were also upregulated for the cells cultured on specimen S as compared to those on specimen L. The osteoconductivity of specimen S was superior to that of specimen L four weeks after implantation in calvarial defects of New Zealand white rabbits. Taken together, it can be concluded that the hydroxyapatite with a small grain size, which had high numbers of grain-boundaries per unit area, had a strong osteogenic capacity compared with the hydroxyapatite with a large grain size due to its high surface energy, which enriched the adsorption of serum proteins.

Authors : Fumiko Nishio (1,2), Isao Hirata (1), Kazuhiro Tsuga (2), Koichi Kato (1)
Affiliations : (1) Department of Biomaterials; (2) Department of Advanced Prosthodontics, Graduate School of of Biomedical & Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan

Resume : Bioadhesive polymeric hydrogels capable of firm adhesion to various biological tissues have acquired considerable attention due to their significance in medicine and dentistry. Thus far many types of bioadhesive hydrogels have been investigated using different polymers such as polyacrylates, poly(ethylene glycol)s, and the derivatives of polysaccharides and proteins, while less attention has been paid to polyamphoteric properties of crosslinked polymer networks. The aim of this study is to investigate the bioadhesive properties of polyamphoteric hydrogels synthesized by copolymerizing acrylic acid (AAc) with N,N-dimethylaminopropyl acrylamide (DMAPAA) in the presence of N,N'-methylene-bis-acrylamide (MBA). Tissue adhesion of hydrated gels was evaluated in vitro using the excised porcine intestine as a substrate, and the data were compared with that measured for the pure poly(acrylic acid) (PAAc) hydrogel that is a bioadhesive system most-extensively studied ever. In this study, we will demonstrate that incorporation of a small fraction of the cationic monomer, DMAPAA, to a PAAc hydrogel produces the polyamphoteric hydrogel that exhibits firm adhesion toward mucosa. The adhesion enhancement by cation incorporation will be discussed in terms of the network structure of the polyamphoteric hydrogels and its nanoscale dynamics leading to firm interactions between polymer segments and mucosal components.

Authors : Yuka Yamauchi (1,2), Kotaro Tanimoto (2), Koichi Kato (1)
Affiliations : (1) Department of Biomaterials; (2) Department of Orthodontics and Craniofacial Developmental Biology, Graduate School of Biomedical & Health Sciences, Hiroshima University, Hiroshima, Japan

Resume : Neural progenitor cells (NPCs) have potential to differentiate into three major cells in central nervous system (CNS). Although these cells are considered to be a promising source for stem cell-based regenerative therapy for CNS disorders, a novel technology is still required to efficiently produce a pure population of NPCs in large quantity. For this challenge, we made an attempt to molecularly design the surface of culture substrates, taking advantage of an ability of epidermal growth factor (EGF) that can specifically interact with NPCs to promote these cells to proliferate. In this study, EGF was immobilized onto the surface of glass-based substrate. On the other hand, NPC-containing neurospheres were obtained by culturing mouse induced pluripotent stem (iPS) cells in suspension in the presence of soluble EGF and basic fibroblast growth factor. The neurospheres were dissociated into single cells and seeded to the EGF-immobilized substrates. It was observed that neurosphere-forming cells seeded and cultured on the EGF-immobilized surface formed a 2-dimensional cellular network that is characteristic of NPCs. The number of cells increased approximately 9 folds after 3-day culture on the substrate, demonstrating that the substrate enable us to efficiently expand NPCs derived from iPS cells.

Authors : Hsi-Chin Wu1, 2*, Jing-Yun Lin2, Tzu-Wei Wang3, Jui-Sheng Sun4
Affiliations : 1 Department of Bioengineering, Tatung University, Taiwan; 2 Department of Materials Engineering, Tatung University, Taiwan; 3 Department of Materials Science and Engineering, National Tsing Hua University, Taiwan; 4 Department of Orthopedic Surgery, National Taiwan University Hospital, Taiwan

Resume : The effectiveness of cancer therapy relies on delivering therapeutic agent specifically and recognizing of target site precisely. These two factors play a vital role in optimizing the treatment outcome while minimizing side effects. In this study, we demonstrate that iron-doped hydroxyapatite nanocrystals with mesoporous structure (MPmHAp) are successfully prepared through one-pot synthesis process. The size of MPmHAp is 60-80 nm in length and 10-20 nm in width with short rod-like morphology. These MPmHAp not only demonstrate mesoporous structure, high surface to volume ratio for efficient drug loading capacity, but also have good cell biocompatibility. When PEG-conjugated HER2 being modified onto MPmHAp, these nanocrystals can specifically target to tumor site. Also, they possess superparamagnetic property and show controlled drug release profile through magnetic triggering. MPmHAp nanocrystals can further generate heat under applied alternative magnetic field. These results indicate that the PEG-HER2 coated MPmHAp nanocrystals show great potential as novel delivery carrier for the application in chemotherapy.

Authors : Se Won Bae, Seunghan Shin
Affiliations : Green Chemistry and Materials Group, Korea Institute of Industrial Technology, Cheonnan, Republic of Korea

Resume : Hydrogels are water-swollen polymer networks that have found a range of applications from drug delivery to regenerative medicine. Historically, their design has consisted mainly of static systems and those that undergo simple degradation. However, advances in polymer synthesis and processing have led to a new generation of dynamic systems that are capable of responding to artificial triggers and biological signals with spatial precision. These systems will open up new possibilities for hydrogels as model biological structures and in tissue regeneration. In this presentation, we will report the evolution of hydrogel design towards dynamic behavior and particularly emphasize recent developments in hydrogel design that offer the ability to precisely control trigger-responsive properties.

Authors : Dorsa Dehghan-Baniani (a,b), Reza Bagheri (b), Atefeh Solouk (c), Hongkai Wu (a,d,*) * Corresponding Author
Affiliations : (a) Department of Chemical and Biological Engineering, Division of Biomedical Engineering, The Hong Kong University of Science and Technology, Hong Kong, China (b) Polymeric Materials Research Group, Department of Materials Science and Engineering, Sharif University of Technology, Tehran, P.O. Box 11155-9466, Iran (c) Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran. (d) Department of Chemistry, The Hong Kong University of Science and Technology, Hong Kong, China. and HKUST Shenzhen Research Institute, Shenzhen, China

Resume : Repairing cartilage defects remains challenging due to its sophisticated properties and limited regeneration capacity. To address this, we developed an injectable thermosensitive hydrogel based on chitosan, which can be administered to the site of injury non-invasively. This hydrogel is able to provide long-term release of two drugs with different therapeutic effects including kartogenin (KGN), a small molecule which promotes chondrogenesis and diclofenac sodium (DS) which is commonly used as an anti-inflammatory drug. More importantly, this hydrogel offers high storage shear modulus (167±5 kPa) which is desired for cartilage tissue engineering and fast gelation at 37 ?C upon injection to the injury site (5±0.5 min). To achieve such properties, chitosan was chemically modified with maleimide, and for further enhancement of the hydrogel?s mechanical performance, DS-loaded halloysite nanotubes (HNTs) were used as reinforcements in the hydrogel. In addition, KGN was encapsulated in the starch microspheres by a droplet microfluidic chip for chondrogenic differentiation of human adipose mesenchymal stem cells (hAMSCs) which were further incorporated in the hydrogel. Results confirmed that the hAMSCs treated with KGN-loaded microspheres showed enhanced chondrogenic differentiation compared to pure KGN. Also, further incorporation of the microspheres within the hydrogel, increased chondrogenic differentiation of hAMSCs significantly. We believe that this innovative hydrogel shows promising capability to be used for cartilage tissue engineering applications.

Authors : Oh Hyeong Kwon, Donghwan Cho, Won Ho Park, and Sang-Hoon Rhee
Affiliations : Kumoh National Institute of Technology; Chungnam National University; Seoul National University

Resume : Bone tissue engineering aims regeneration of defected biological bones by combining cells, scaffolds, and growth factors. However, growth rate of bone tissue components are slower than adjacent soft tissues. Therefore, defected bone tissues are required a barrier membrane and a guiding scaffold for intact restoration of a target tissue. Here, we prepared patient-customizable guided bone regeneration (GBR) membrane-guided tissue regeneration (GTR) scaffold hybrid constructs for precise bone tissue restoration without dimensional collapse. Poly(glycolic acid) (PGA) scaffolds (100 - 800 µm in pore diameter) were fabricated by hot melt additive manufacturing method. Silk fibroin nanofiber membranes were prepared by electrospinning method. The microstructure of silk fibroin nanofiber and PGA scaffolds was observed by SEM. Compressive modulus of PGA scaffolds was measured using UTM. Biodegradability of silk fibroin nanofiber membranes and PGA scaffolds was investigated in PBS for 8 weeks. Initial attachment and proliferation of preosteoblasts on a PGA scaffold was analyzed by seeding efficiency and MTT assay. In vivo animal study was performed using rabbit calvarial defect model for 8 weeks. Regenerated tissues were visualized by Masson Trichrome staining. Regenerated bone volume was calculated by micro-computed tomography. The silk fibroin-PGA hybrid scaffold group showed significant regeneration of bone tissue compared to control groups. The silk fibroin nanofiber-PGA scaffold hybrid construct will provide a prospective approach as a GBR-GTR agent.

Authors : Zied Ferjaoui 1 , Raphaël Schneider 2 , Eric Gaffet 1 and Halima Alem 1
Affiliations : 1 Institut Jean Lamour (IJL), UMR CNRS 7198, Université de Lorraine, Department N2EV, Parc de Saurupt CS50840 54011 Nancy, France. 2 Laboratoire Réactions et Génie des Procédés (LRGP), UMR CNRS 7274, Université de Lorraine, 1 rue Grandville 54001 Nancy, France

Resume : The development of nanoparticulate systems able to serve as efficient diagnostic and/or therapeutic tools against sever diseases have emerged as an emerging research area in nanomedicine those last two decades. They have effectively shown fascinating results in diseases such as cancer, infectious or neurodegenerative disorder. Especially for cancer treatment, most powerful diagnosis toll is MRI (Magnetic Resonance Imaging). To enhance MRI images interpretation, contrast agents were developed to clarify images as Superparamagnetic iron oxide (SPIO) nanoparticle. They have indeed received a great attention since their development as a liver contrasting agent 20 years ago1. Furthermore, their nanoparticulate properties represented by the nanosized dimension and shape allow different biodistribution and opportunities beyond the conventional imaging of chemical agents. Coating those biocompatible NPs by a smart polymer shell that can ensure not only a better stability of the nanomaterials in the body but also enhance their biodistribution and new functionalities which make them ideal candidates for medicinal applications2. Two family of nanoparticles were synthesized, the first one consist in superparamagnetic Fe3O4 nanoparticules functionalized by a biocompatible responsive copolymer based on 2-(2-methoxy) éthyl méthacrylate (MEO2MA), oligo (ethylene glycol) methacrylate (OEGMA), which lead to Fe3O4@P (MEO2MAx-OEGMAy). The second family consists in the same nanoparticles were the folic acid was grafted at the chain end to target Fr-? receptors at the surfaces of some cancer cells. The core/shell nanostructures were completely microscopic and spectroscopic methods and their whole behavior in water and physiological media with temperature was completely monitored. We could then demonstrate the efficiency of the process to lead to responsive core/shell nanoparticles. We could show that the magnetic properties of the core/shell Fe3O4 based nanostructures, only the amount of the grafted polymer plays a role on the saturation magnetization of the NPs, and no influence of the aggregation was evidenced. The drug release experiments confirmed that Doxorubicine (model cancer drug) can be loaded and largely released above the co-polymer LCST (around 40°C). From the results obtained, it can be concluded that our new nanomaterials can be considered for further use as multi-modal cancer therapy tools. (

Authors : Minsuk Choi, Seung J. Yu, Yoonjung Choi, Hak R. Lee, Eunbeol Lee, Eunjung Lee, Yumi Lee, Junhyuk Song, Jin G. Son, Tae G. Lee, Jin Y. Kim, Sukmo Kang, Jieung Baek, Daeyoup Lee, Sung G. Im, and Sangyong Jon
Affiliations : Department of Chemical and Biomolecular Engineering, Korea Advanced Institute of Science and Technology

Resume : Although cancer stem cells (CSC) are thought to be responsible for tumor recurrence and resistance to chemotherapy, CSC-related research and drug development have been hampered by the limited supply of diverse, patient-derived CSC. Here, we present a functional polymer thin film (PTF) platform that promotes conversion of cancer cells to highly tumorigenic three-dimensional (3D) spheroids without the use of biochemical or genetic manipulations. Culturing various human cancer cells on the specific PTF, poly(2,4,6,8-tetravinyl-2,4,6,8-tetramethyl cyclotetrasiloxane) (pV4D4), gave rise to numerous multicellular tumor spheroids within 24 hours with high efficiency and reproducibility. Cancer cells in the resulting spheroids showed a significant increase in the expression of CSC-associated genes and acquired increased drug resistance compared with two-dimensional monolayer-cultured controls. These spheroids also exhibited enhanced xenograft tumor-forming ability and metastatic capacity in nude mice. By enabling the generation of tumorigenic spheroids from diverse cancer cells, the surface platform described here harbors the potential to contribute to CSC-related basic research and drug development.

Authors : A. Visan1, G.Popescu-Pelin1, I. Zgura2,M. Chiritoiu3, L. E. Sima3, Mihai Cosmin Cotru?5, R. Cristescu1, G. Socol1
Affiliations : 1 National Institute for Lasers, Plasma and Radiation Physics, Magurele, Ilfov, Romania 2 National Institute of Materials Physics, Magurele, Ilfov, Romania 3 Department of Molecular Cell Biology, Institute of Biochemistry, Romanian Academy, Bucharest, Romania 4Institute of Cellular Biology and Pathology ?N. Simionescu,? 8, BP Hasdeu Street, Bucharest, Romania 5University Politehnica of Bucharest, Faculty of Material Science and Engineering, Department of Metallic Materials Science, Physical Metallurgy, 313, Splaiul Independen?ei street, Building J, 060042 -Bucharest, Romania

Resume : Composite thin films based on polycaprolactone-polyethylene glycol (PCL-PEG) polymeric blends employed in medical application, with convenient mechanical strength and corrosion behavior, controllable hydrophilicity/ wettability and degradability were deposited by dip coating technique. The present study analyzes long term in vitro degradation profile of simple and composite films in dynamic flux of simulated body fluid. The obtained biological results proved that the thin films stimulate and support tissue growth.We identify the effect of PEG incorporation on the biodegradation characteristics of more stable PCL. Static water contact angles measurement indicated that hydrophilicity of the composite films containing more PEG has improved considerably. It has been shown that the degradation of PCL-PEG blends increase with a decreasing crystallinity of the PEG, and can be controlled by adjusting the component ratio of the blends. It was found that the degradability of the polycaprolactone was improved by introducing a PEG component into it. The degradation of PCL -PEG copolymer increase with a decreasing crystallinity of the copolymer, and can be controlled by adjusting the component ratio of the copolymer.

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Biointerfaces at electrodes I : Mathieu Etienne
Authors : Seiya Tsujimura
Affiliations : Division of Materials Science, Faculty of Pure and Applied Sciences, University of Tsukuba

Resume : Electro-enzymatic reactions combining oxidoreductase and electrode reactions allow highly selective electrochemical oxidation/reduction reactants under mild reaction conditions, with a very small overpotential. Ezymatic biofuel cells (EBFCs), which convert chemical energy of the oxidation of carbohydrates, such as glucose, in combination with oxygen reduction, under mild condition, come to attract considerable attention as power sources for wearable devices or self-powered sensor-node systems. A combination of electron transfer technology and porous carbon material would be helpful in achieving a much higher and stable current output, thus contributing to a practical advance in the sustainable energy field. Recent developments in EBFCs technology using porous carbon materials, especially Magnesium oxide (MgO)-templated porous carbons (MgOC), are highlighted. To realize high current density per geometric surface area, the concentration of buffer solution should be increased to prevent the local pH change during the electro-enzymatic reaction and also to minimize the ohmic solution resistance in the cell. I will show the effect of characteristics and concentration of electrolyte on the electroenzymatic reaction.

Authors : Andrew J. Gross?, Jules L. Hammond?, Xiaohong Chen?, Fabien Giroud?, Christophe Travelet?, Redouane Borsali?, Serge Cosnier?
Affiliations : ? Université Grenoble Alpes, CNRS, DCM, 38000 Grenoble, France ? Université Grenoble Alpes, CERMAV, 38000 Grenoble, France

Resume : Enzymatic biofuel cells are eco-friendly power sources that can generate electrical energy (µW-mW) from renewable chemical substrates such as glucose and oxygen, but their stability is a major issue [1]. We report here the characterization and bioelectrocatalysis of ?sweet? redox-active cyclodextrin-coated nanoparticles as electron shuttles [2,3]. We depart from the traditional use of immobilized redox molecules and polymers and instead explore the use of solubilized redox nanoparticles and enzymes in solution for mediated bioelectrocatalysis. This approach can offer possibilities such as refueling, higher biocatalyst concentrations compared to immobilisation methods, size exclusion principles to avoid cross-reactions, and dynamic reactivity based on diffusion and rotation. We will provide spectroscopic and electrochemical data which reveals the controlled self-assembly of nanoparticles with host-guest functionality that can integrate insoluble redox species in aqueous buffer solutions [2-4]. The use of different nanoparticles with bilirubin oxidase and FAD-dependant glucose dehydrogenase enzymes will be demonstrated and compared with classical systems for oxygen reduction and glucose oxidation, respectively. Finally, the new SEFC-carbon nanotube buckypaper biodevice and its use for long-term quasi-continuous power generation will be demonstrated [3,5]. It is feasible that SEFCs, in combination with a boost converter, could be exploited as a new generation of green power sources for low-power electronics such as lab-on-a-chip sensing and data transmission devices.

Authors : Guomin Wang, Huaiyu Wang, Paul K. Chu
Affiliations : Guomin Wang, Paul K. Chu, Department of Physics and Department of Materials Science and Engineering, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, P. R. China Huaiyu Wang, Research Center for Biomedical Materials and Interfaces, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Shenzhen, 518055, P.R. China.

Resume : Electrical interactions between bacteria and the environment are delicate and essential [1][2]. For instance, by means of electron transfer, bacteria complete respiration on the cell membrane to supply energy for cell growth, proliferation, and maintenance and disturbing electron transfer in bacteria can raise the production of reactive oxygen species (ROS) to hinder growth. In this study [3], an external electrical current is applied to capacitive titania nanotubes doped with carbon (TNT-C) to evaluate the effects on bacteria killing and the underlying mechanism is investigated. When TNT-C is charged, post-charging antibacterial effects proportional to the capacitance are observed. This capacitance-based antibacterial system works well with both direct and alternating current (DC, AC) and the higher discharging capacity in the positive DC (DC ) group leads to better antibacterial performance. Extracellular electron transfer observed during early contact contributes to the surface-dependent post-charging antibacterial process. Physiologically, the electrical interaction deforms the bacteria morphology and elevates the intracellular reactive oxygen species level without impairing the growth of osteoblasts. This is the first systematic study on the post-charging antibacterial properties of biomaterials with tunable capacitance. Our finding spurs the design of light-independent antibacterial materials and provides insights into the use of electricity to modify biomaterials to complement other bacteria killing measures such as light irradiation. References [1] G. M. Wang, H. Q. Feng, et al. ACS Applied Materials and Interfaces, vol. 8, no. 37, pp. 24509 ? 24516 (2016). [2] G. M. Wang, W. H. Jin, et al. Biomaterials, vol. 124, pp. 25 ? 34 (2017). [3] G. M. Wang, H. Q. Feng, et al. Nature Communications, vol. 9, Paper 2055 (2018).

Authors : Chiung Wen Kuo, and Peilin Chen
Affiliations : Research Center for Applied Sciences, Academia Sinica, Taiwan.

Resume : In this study, we employed a novel one step electrospinning process to fabricate poly(ethylene oxide) (PEO)/poly(3,4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS) core/shell nanofiber structures with improved water resistance and good electrochemical properties. We then integrated a biocompatible polymer coating with three-dimensional (3D) PEDOT-based nanofiber devices for dynamic control over the capture/release performance of rare circulating tumor cells (CTCs) , as well as the label-free detection by using organic electrochemical transistors (OECTs). The detailed capture/release behavior of the circulating tumor cells was studied using an organic bioelectronic platform comprising PEO/PEDOT:PSS nanofiber mats with 3 wt % (3-glycidyloxypropyl)trimethoxysilane as an additive. We have demonstrated that these nanofiber mats deposited on five-patterned indium tin oxide finger electrodes are excellent candidates for use as functional bioelectronic interfaces for the isolation, detection, sequential collection, and enrichment of rare CTCs through electrical activation of each single electrode. This combination behaved as an ideal model system displaying a high cell-capture yield for antibody-positive cells while resisting the adhesion of antibody-negative cells. Taking advantage of the electrochemical doping/dedoping characteristics of PEDOT:PSS materials, the captured rare cells could be electrically triggered release through the desorption phenomena of PLL-g-PEG-biotin on device surface. More than 90% of the targeted cancer cells were captured on the 3D PEDOT-based nanofiber microfluidic device; over 87% of captured cancer cells were subsequently released for collection; approximately 80% of spiked cancer cells could be collected in a 96-well plate. For the OECT design, it was demonstrated for monitoring CTC-capture performance and identifying cancer cell phenotypes. This 3D PEDOT-based bioelectronic device approach appears to be an economical route for the large-scale preparation and detection of systems for enhancing the downstream characterization of rare CTCs.

10:15 Coffee break    
11:15 Plenary Session 1    
12:30 Lunch    
Biointerfaces at electrodes II : Frederic Barriere
Authors : Nicolas Brun
Affiliations : Institut Charles Gerhardt Montpellier, UMR 5253, CNRS, Université de Montpellier, ENSCM

Resume : The interaction of biomolecules with solid surfaces ? in particular, carbon surfaces ? has been of great interest for both fundamental and applied aspects. The diversity of carbon allotropes gives access to a large variety of structural and textural properties, while the complexity of biomolecules (e.g. polysaccharides, cofactors, proteins) provides specific functionalities. In this presentation, I will discuss few examples of biomolecule-carbon interfaces for the design of functional materials. In a first example, I will present the preparation of aqueous colloidal suspensions obtained via the co-dispersion of multi-walled carbon nanotubes (MWCNTs) and polysaccharides, e.g. cellulose. Such dispersions were successfully employed to stabilize oil-in-water (smart) interfaces and elaborate hierarchical composite structures, e.g. lace-like hollow spheres. In a second example, I will introduce the importance of biomolecule-carbon interfaces in enzymatic catalysis and electrocatalysis, via pore confinement and surface modification. In our group, a particular attention has been given to formate dehydrogenases (FDHs), which require the loosely bound cofactor nicotinamide adenine dinucleotide (NAD). We recently developed carbon-based flow through enzymatic reactors for the production of formate from carbon dioxide and a novel method to covalently immobilize NAD onto carbonaceous materials.

Authors : Ana Domínguez-Bajo1, Ankor González-Mayorga2, Beatriz L. Rodilla3, Ana Arché3, Lucas Pérez3, María Teresa González3, Elisa López2,4, and María Concepción Serrano1,*, *Correspondence author:
Affiliations : (1) Instituto de Ciencia de Materiales de Madrid, Consejo Superior de Investigaciones Científicas (ICMM-CSIC), Calle Sor Juana Inés de la Cruz 3, 28049 Madrid, Spain; (2) Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla-La Mancha, Finca La Peraleda s/n, 45071 Toledo, Spain; (3) IMDEA Nanociencia, Calle Faraday 9, Campus Cantoblanco, 28049 Madrid, Spain; (4) Research Unit of ?Design and Development of Biomaterials for Neural Regeneration?, Hospital Nacional de Parapléjicos, Joint Research Unit with CSIC, 45071 Toledo, Spain.

Resume : Despite research and clinical efforts of the last decades, there is no cure for spinal cord injury to date. Remarkable drawbacks of this type of lesions include dramatic changes in the quality of life and life expectancy of patients, affected by a disruption of neural connections through the spinal cord. Aiming to provide more effective therapeutic alternatives, neuroscience, nanotechnology, and materials science are working together on the development of novel biocompatible implants capable of improving the functionality of the damaged neural tissue at the lesion. In the ByAxon Project, we have developed a new generation of 2D nanoelectrodes consisted of vertically arranged metal nanowires (NWs) made of Ni and Au and grown by template-assisted electrodeposition over a flexible gold base. The behavior of neural progenitor cells isolated from rat embryos has been studied in culture on these substrates with focus on cell adhesion, viability, morphology, and differentiation. Neural cells properly adhere and spread, closely interacting with the metallic NWs. After 2 weeks, these cells are able to form dense neural networks with high viability and mainly composed of neurons. These results encourage further research in the use of these materials as stimulating nanoelectrodes for the development of a local bypass directly working at the spinal cord. This project is funded by the European Union?s Horizon 2020 research and innovation programme under grant agreement No 737116.

Authors : Stéphane PINCK, Frédéric P.A. JORAND, Mengjie XU, Mathieu ETIENNE
Affiliations : Université de Lorraine, CNRS, LCPME, F-54000 Nancy, France.

Resume : The concept to artificially reconstitute an electroactive biofilm is a recent strategy used in order to optimize extracellular electron transfer (EET) reactions and mimic natural biofilms [1-3]. Those artificial biofilms would greatly benefit to electrochemical bacterial devices such as microbial fuel cell or sustain biosensors. They would also benefit to microbial electrosynthesis or electrocatalysis. Recent studies have reported the application of microbial electrochemical systems in biochemical production of ethanol or hydrogen and to the bioremediation of sulphate or nitrogen species in aqueous environment. In this work, we studied the direct electron transfer reactions occurring in a biocomposite resulting from the self-assembly of microbes with carbon nanomaterials and proteins. Both bacteria and yeast cells have been evaluated. For example, with Shewanella oneidensis MR1, the onset potential observed for fumarate electroreduction was found very close to 0.030 V vs. SHE, the formal redox potential for fumarate/succinate interconversion and a maximum current density in the range of 1 A m-2 was reached with this electroactive artificial biofilm. In this communication, we will describe and discuss this new way to promote direct electron transfer reactions in electroactive artificial biofilms. [1] S. Pinck et al., Bioelectrochemistry, 118 (2017) 131?138. [2] S. Pinck et al., Bioelectrochemistry, 124 (2018) 185?194. [3] S. Pinck et al., ChemElectroChem, revision submitted. This work was supported by the French PIA project « Lorraine Université d?Excellence », reference ANR-15-IDEX-04-LUE.

Authors : L. Bettamin[1] [2], A. Casanova[1], M-C. Blatche[1], F. Mathieu[1], K. Bourgade[2], H. Martin[2], E. Suberbielle[2], D. Gonzalez-Dunia[2], G. Larrieu[1]
Affiliations : [1]LAAS-CNRS, Université de Toulouse, CNRS, Toulouse, France [2]CPTP, INSERM UMR 1043, CNRS UMR 5282, Université de Toulouse, Toulouse, France

Resume : A major challenge for bioelectronics lies in the monitoring of electrical activities of neurons at the single cell level, both with high resolution of measure and applied simultaneously to multiple locations. One breakthrough is the development of a new class of devices that take advantage of miniaturization in electronics, thereby refining the investigation resolution. Here, we present a bio-platform with 3D passive nanoprobes based on nanostructures with very high surface-to-volume ratio. The device is created using a large-scale fabrication process based on conventional silicon processing. The electrodes are composed of several nanowires, where the design (size, pitch …) has been optimized to favour the engulfment of the cell. We demonstrate that the surface engineering of the probes at nanoscale leads to drastic reduction in the electrode impedance. This key factor is able to enhance the signal resolution 200-fold when compared to conventional MEA planar technology. We could register spontaneous activity of primary rat neurons with record amplitudes, not only for action potentials (ten of mV), but also smaller signals (Pre- and Post-Synaptic Potentials (PSPs)) usually invisible with planar MEAs. Moreover, we present the impact on neuronal activity of several chemical stimulations (chemical blockers and Long Term Potentiation inducers), as well as of molecules involved in Alzheimer’s disease (Amyloid Beta Peptide).

Authors : Beatriz L. Rodilla (1,2), Claudia Fernández-González (1,2), Ana Arché (1), Ana Domínguez-Bajo (3), Ankor González-Mayorga (4), Elisa López-Dolado (4), Sandra Ruiz-Gomez (2), Julio Camarero (1,5), Rodolfo Miranda (1,5), María Concepción Serrano (3), Lucas Pérez (1,2), María Teresa González (1)
Affiliations : (1) IMDEA Nanociencia, Campus Cantoblanco, 28049 Madrid, Spain; (2) Depto. Física de Materiales. Universidad Complutense de Madrid, 28040, Madrid, Spain; (3) Instituto de Ciencia de Materiales de Madrid (ICMM-CSIC), 28049 Madrid, Spain; (4) Hospital Nacional de Parapléjicos, Servicio de Salud de Castilla-La Mancha, 45071 Toledo, Spain; (5) Depto. Física de la Materia Condensada-IFIMAC. Universidad Autónoma de Madrid, 28049, Madrid, Spain

Resume : Science is facing the challenge of directly interact with neural tissues to perform electrical stimulation of the neural activity in zones that have been compromised. Spinal cord stimulators, cortical electrodes or retina implants, are some of the devices inspired by this technology. These electrode-based devices nowadays present size, morphology and rigidity issues that unleashes an immunologic response that inactivates them. We are developing new biocompatible flexible electrodes with nanostructured surface. They are composed by a flexible Au thin sheet with one of its surfaces covered by a network of metallic vertical NWs. The aspect-ratio of the NWs ensures high contact with neural tissue and their size in the nanoscale minimises the damage. We obtain our structures depositing metals using template assisted electrodeposition. We can vary the diameter, length and material (Au, Ni, Fe...) of our NWs. We can also produce core/shell metallic NWs using pulsed electrodeposition, choosing the material of both, the core and shell. As example, we present Ni/Au core/shell electrodes, in which the Ni of the core conferees robustness to the NWs, and the Au of the shell ensures a high electrical conductivity and good biocompatibility. The positive results of the biocompatibility studies support the potential and viability of our electrodes as functional electrical stimulating devices. This project has received funding from the EU Horizon 2020 R&I programme under grant agreement 737116.

Authors : Luisa Torsi,1,2,3* Eleonora Macchia,1 Rosaria Anna Picca,1,2 Kyriaki Manoli,1 Cinzia Di Franco,4 Nicola Cioffi,1,2 Ronald Österbacka,3 Gerardo Palazzo1,2 and Gaetano Scamarcio,4,5
Affiliations : 1Dipartimento di Chimica - Università degli Studi di Bari “Aldo Moro” - Bari (I) 2CSGI (Centre for Colloid and Surface Science) – Bari (I) 3Center for Functional materials, The Faculty of Science and Engineering - Åbo Akademi University – Turku (FI) 4CNR - Istituto di Fotonica e Nanotecnologie, Sede di Bari (I) 5Dipartimento Interateneo di Fisica “M. Merlin” - Università degli Studi di Bari – “Aldo Moro” - Bari (I) *

Resume : Among the single-molecule detection methods proposed so far, only a few are exploitable for real clinical sensing. Large-area organic-bioelectronics is emerging as a cross-disciplinary research field for the development of a platform capable of selective, label-free and fast biomarker detection at the physical limit in real biofluids. A mass-manufacturable platform with such characteristics holds the potential to bring precision medicine into the everyday medical practice, revolutionizing our current approach to clinical analysis. This lecture aims at critically prioritize the main technologies for single-molecule detection. Scrutinized figures-of-merit include, besides limit-of-detection and selectivity, feasibility of operation in real-fluids, time-to-results and cost-effectiveness. Electrolyte-Gated Field-Effect-Transistors (EG-FETs) [1-4] with a bio-functionalized large-area sensing gate, appear as very promising, also over organic-electrochemical-transistor. The material science and the devices operational aspects underpinning EG-FETs unprecedented sensing performance, including the role of the cooperative hydrogen-bonding network and the gate-channel strong capacitive coupling, are discussed. References 1. Macchia, E., Manoli, K., Holzer, B., Di Franco, C., Ghittorelli, M., Torricelli, F., Alberga, D., Mangiatordi, G.F., Palazzo, G., Scamarcio, G., Torsi, L. Single molecule detection with a millimetre-sized transistor. Nature Communications 9, 3223 (2018). 2. Nature highlights - Selections form the scientific literature. Nature 560, 412 (2018). 3. Macchia, E., Tiwari, A., Manoli, K., Holzer, B., Ditaranto, N., Picca, R.A., Cioffi, N., Di Franco, C., Scamarcio, G., Palazzo, G., Torsi, L. Label-free and selective single-molecule bioelectronic sensing with a millimeter-wide self-assembled monolayer of anti-immunoglobulins. Chemistry of Materials in press (2019) 4. Macchia, E., Manoli, K., Holzer, B., Di Franco, C., Picca, R., Cioffi, N., Scamarcio, G., Palazzo, G., Torsi, L. Selective Single-Molecule Analytical Detection of C-Reactive Protein in Saliva with an Organic Transistor. Analytical and Bioanalytical Chemistry in press (2019).

15:45 Coffee Break    
Biointerfaces for implantable medical devices : Giovanni Marletta
Authors : Reza Shahbazian-Yassar(1)*, Tolou Shokuhfar(2)
Affiliations : (1) Associate Professor, Department of Mechanical Engineering, University of Illinois at Chicago, Chicago, IL 60607, USA. *Email: (2) Associate Professor, Department of BioEngineering, University of Illinois at Chicago, Chicago, IL 60607, USA.

Resume : This talk will provide an overview of the PIs' efforts to understand the dynamics of biomineralization via in-situ transmission electron microscopy. First we demonstrate how to utilize graphene sheets to build a liquid-cell nanoreactor that fits the chamber of high-resolution TEM. Graphene is impermeable to liquids such as aqueous solutions and therefore can be used to seal liquid solutions from leaking to the high vacuum of TEM environment. In addition, the excellent electrical conductivity of graphene and its ability to scavenge the radicals produced by the interaction of electron beam and liquid solutions provide an excellent platform to perform imaging of biological or hydrated specimens. We then demonstrate our success to observe the biomineralization of hydroxyapatite (HA) crystals. Our results show that HA crystals follow classical and non-classical nucleation theories to from within a supersaturated solution. The solution initially goes through ion-rich and ion-poor liquid-liquid phase separation. Amorphous calcium phosphate (ACP) acts as template for the biomineralization of HA while HA can also form by aggregation of primary HA nanoparticles. We also studied the effect of molecular modifiers on the effect of calcium oxalate crystals that are the primary constituent of kidney stones. We show that the addition of citrate can affect the crystallization pathway of these minerals. Interestingly, the citrate molecules affect the pre-nucleation stage of CaOx crystals making them thermodynamically stable. In addition, the addition of citrate reduces the stability of calcium oxalate monohydrates. In addition, we will showcase some examples of biomineralization of iron oxide core in ferritin proteins and demonstrate the ability to monitor the biomineralization of these crystals using graphene liquid cells in TEM. We will show that the ratio of L and H subunits in the ferritin protein shells can affect the nucleation and growth of iron oxide cores. We also will present our latest results on the biomineralization of magnetosomes in magnetotactic bacteria grown in iron-rich media using in situ GLC-TEM studies. We observed that such bacteria can remain alive and intact during TEM imaging and follows the classical nucleation theory for the biomineralization of magnetosomes.

Authors : P. Ivanchenko (a), M. Iafisco (b), A. Tampieri (b), P. Ugliengo (a) and G. Martra (a)
Affiliations : a) Department of Chemistry and Interdepartmental Centre NIS, University of Torino, Via P. Giuria 7, 10125 Torino -Italy b) Institute of Science and Technology for Ceramics (ISTEC), National Research Council (CNR), Via Granarolo 64, 48018 Faenza - Italy

Resume : Nanohydroxyapatite (nanoHA) are key materials for bone tissue healing, and their functional behavior is ruled in large extent by nature and structure of sites exposed at their surfaces. Relevant challenges are well beyond the recognition of crystallographic facets limiting nanoparticles: for nanoHA the most abundant terminations are just of one type, namely (010), but the atomic structure they expose can be of three types: stoichiometric, Ca-rich and P-rich [1]. These important features are often elusive by direct microscopy imaging, in particular the assessment of their relative amount. Moreover, is there any effect of these different terminations on the causal sequence proposed by Kasemo [2]: atomic surface structure/ surface hydration states/ states of adsorbed proteins/ responses elicited in cells? To contribute to solve this issue, we implemented a synergic loop between preparation of nanoHA in controlled conditions and elucidation of their surface features and interfacial behavior, at molecular level, by combining the experimental study of adsorbed molecules, by in-situ IR spectroscopy, with quantum mechanical modeling of adsorption events, demonstrating the impact of the ratio between (010)_Ca-rich and (010)_P-rich terminations on the structure of adsorbed water multilayers, and on the conformation of an adsorbed protein used as ?probe?, namely bovine serum albumin. [1] R. Astala and M. J. Stott, Phys. Rev. B 78 (2008) 075427 [2] B. Kasemo, Surf. Sci. 500 (2002) 656?677

Authors : A. Bonciu1, V. Dinca1, M. Icriverzi2,3, S. Brajnicov1, L. Rusen1, A. Roseanu2, A. Campean3 and M. Dinescu1
Affiliations : 1National Institute for Lasers, Plasma and radiation Physics, Bucharest, Romania 2Institute of Biochemistry of the Romanian Academy IBAR, Bucharest, Romania 3University of Bucharest, Faculty of Biology, Bucharest, Romania 4University of Bucharest, Faculty of Physics, Bucharest, Romania

Resume : In the field of biodevices functionalization, especially for bone implants, active compounds such as ceramics and/or proteins are used for enhancing cellular response. The control on the distribution of ceramic nanoparticles such hydroxyapatite (HA) and Lactoferrin (LF) could significantly influence the cellular response at nano-composites interfaces, as well as the final application towards implants application. Therefore, this work is focused on embedding HA spherical nanoparticles and lactoferrin (LF) within synthetic biodegradable copolymers Poly(ethylene glycol)- block-poly(?-caprolactone) methyl ether (PEG-block-PCL Me) for the preparation of new nanocomposites coatings targeting the modulated response of macrophages and osteoblast cells (i.e adhesion, mineralization). The controlled incorporation of HA and LF within the synthetic copolymeric substrates was performed by matrix assisted pulsed laser evaporation (MAPLE) method using a modular target system. The resulting morphologies and the main features were studied by Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). Fourier Transform Infrared Spectroscopy (FTIR) data demonstrates that the functional groups in the MAPLE-deposited films remain intact for the individual compounds and that LF was not affected by the solvents used for copolymer. The biofunctionality of the coatings has been tested using the correlated characteristics of the coatings with macrophages and MC3T3- E1 murine osteoblasts response in vitro. The results clearly revealed that the coatings with HA and LF incorporated in the polymeric matrix have enhanced stability as compared with single element coatings, and that the osteoblast behavior (cell adhesion/morphology, proliferation and matrix mineralization) was differentially influenced by the variations in the physicochemical characteristics of materials surface polymeric layers.

Authors : G. Graziani, M. Bianchi, C. Gualandi, M.L. Focarete, G. Pagnotta, M. Carlini, N. Baldini
Affiliations : G. Graziani, IRCSS Istituto Ortopedico Rizzoli, Laboratory of NanoBiotechnology; bOlogna, Italy; M. Bianchi, Fondazione Istituto Italiano di Tecnologia Centro di Neurofisiologia traslazionale, Ferrara (IT) & IRCSS Istituto Ortopedico Rizzoli, Laboratory of NanoBiotechnology, Bologna (IT); C. Gualandi, Department of Chemistry "Giacomo Ciamician", University of Bologna, Bologna (IT); M.L. Focarete, Department of Chemistry "Giacomo Ciamician", University of Bologna, Bologna (IT); G. Pagnotta, Department of Chemistry "Giacomo Ciamician", University of Bologna, Bologna (IT); M. Carlini, Department of Chemistry "Giacomo Ciamician", University of Bologna, Bologna (IT); N. Baldini, IRCSS Istituto Ortopedico Rizzoli, Orthopaedic Pathophysiology and Regenerative Medicine Unit, Bologna (IT) & Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna (IT)

Resume : Nanostructured thin films are extensively studied in orthopedics, to overcome the limitations of medical devices and respond to several clinical needs, such as infection and scarce osseointegration. Here, nanostructured antibacterial and biomimetic films are deposited by Ionized Jet Deposition (IJD), by ablation of silver and deproteinized bone apatite targets, respectively. Coating are mainly proposed for metallic implants, but, because IJD deposition can be carried out without heating the substrate, proof-of-concept of deposition onto heat-sensitive porous substrates (polymeric electrospun patches) is shown. Coatings composition (FT-IR, XRD), morphology (SEM, AFM) and adhesion to titanium substrate (micro-scratch test) are tested. Uniformity of coating, maintenance of fibrous morphology and polymer chemistry of the electrospun substrates are investigated by SEM, TEM and FT-IR. All films exhibit a nanostructured morphology and sub-micrometric thickness, and are composed of nanosized globular aggregates. The morphology and dimensions of the aggregates, as well as the deposition rate, strongly depend on the characteristics of the target. Both silver and bone apatite coatings exhibit a composition closely mimicking that of the deposition target and a high adhesion to the substrate. When deposited on electrospun polymers, the films grow around the fibers, without significantly altering their shape and the porosity of the patch or causing significant damage to the substrate.

Authors : Anita Visan 1, Gianina Popescu-Pelin 1, Oana Gherasim 1,2, Valentina Grumezescu 1,2, Marcela Socol 3, Irina Zgura 3, Camelia Florica 3, Roxana C. Popescu 4, Diana Savu 4, Alina Maria Holban 5, Rodica Cristescu 1, Consuela E. Matei 1, Gabriel Socol 1
Affiliations : 1 National Institute for Lasers, Plasma and Radiation Physics, Magurele, Ilfov, Romania; 2 Department of Science and Engineering of Oxide Materials and Nanomaterials, Faculty of Applied Chemistry and Materials Science, University Politehnica of Bucharest, Bucharest, Romania; 3 National Institute of Materials Physics, Magurele, Ilfov, Romania 4 Life and Environmental Physics Department, Horia Hulubei National Institute of Physics and Nuclear Engineering, Magurele, Ilfov, Romania; 5 Microbiology & Immunology Department, Faculty of Biology, University of Bucharest, Bucharest, Romania;

Resume : Composite thin films of conducting polymer (polyaniline (PANI) grafted Lignin) ? magnetic nanoparticles (Fe3O4) embedded drug (gentamicin sulfate) were deposited by matrix assisted pulsed laser evaporation (MAPLE) technique. Our aim was to obtain the controlled release of the therapeutically active substance, under the action of a magnetic and electric fields for use of these coatings for biomedical applications. It follows that the deposited thin films exhibit a convenient nanostructured surface for bone implants and the unaltered transfer of the initial biomaterials was obtained. The corrosion resistant structures exhibited a significant antibacterial activity against Escherichia coli, Staphylococcus aureus and Candida Albicans strains meanwhile biocompatibility assay (MTT, imunostaining and cellular morphology) demonstrated that the obtained implants are not cytotoxic for bone cells. These results encourage further assessment of this type of biomaterials for their application in controlled drug release at implantation sites by electrical impulse stimulation.

Authors : Roman Major1, Marcin Surmiak2, Juergen M. Lackner3, Michal Charkiewicz5
Affiliations : 1 Institute of Metallurgy and Materials Science, Polish Academy of Sciences, Reymonta St. 25, Crakow, PL. 2 Department of Medicine, Jagiellonian University Medical College, 8 Skawinska Street, 31-066 Cracow, PL. 3 JOANNEUM RESEARCH Forschungsgesellschaft mbH MATERIALS - Institute of Surface Technologies and Photonics Functional Surfaces Leobner Straße 94 A-8712 Niklasdorf 4 ChM sp. z.o.o. Lewickie 3B 16-061 Juchnowiec Ko?cielny Poland

Resume : Jawbone resection is the final surgical treatment for ~5500 patients in EU28 with maxillofacial benign and malignant tumours. The resulting large bone defects lead to scarred, mangled facial appearance and the loss of mastication and speaking function, requiring aesthetic and functional reconstruction as basis for physical and physiologic rehabilitation. Although autologous vascularized bone from fibular or iliac-crest autografts is current gold standard, the portion of transplantable bone is limited and subsequent high-dose anti-cancer chemo-/radiotherapy often results in tissue necrosis. The analysis performed considered the assessment of the impact of 3D printing material on the activation of the genotoxic stress pathway in an in vitro model using human osteoblasts and osteoblast-like cancer cells - SaOS-2. The method of analysis considered micronucleus test and evaluation of the expression of selected genes involved in the genotoxic stress pathway. The expression the determined following genes levels: ATR, MDM2, TP53, PPIA, ATM, CHEK1, CHEK2, CDKN1A. Acknowlegement: This project is implemented under the Program for M-ERA.NET-2016/232/2017 Patient-specific bioactive, antimicrobial PLA-PGA/titanium implants for large jawbone defects after tumour resection ?jawIMPLANT?, funded by the National Centre for Research and Development

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Nanomaterials for biosensing and biodelivery I : Andrew J. Gross
Authors : Victor R. Mann, Sarah Wichner, Alexander Powers, Bruce E. Cohen
Affiliations : The Molecular Foundry, Lawrence Berkeley National Laboratory

Resume : Functionalization of nanocrystals is essential for their practical application to living systems, but synthesis on nanocrystal surfaces is limited by incompatibilities with certain key reagents. The copper-catalyzed azide-alkyne cycloaddition (CuAAC) is among the most useful methods for ligating biomolecules to surfaces, but has been largely useless for semiconductor quantum dots (QDs) because Cu ions quickly and irreversibly quench QD fluorescence. To discover non-quenching synthetic conditions for Cu-catalyzed click reactions on QD surfaces,1 we developed a combinatorial fluorescence assay to screen over 2000 reaction conditions to maximize cycloaddition efficiency while minimizing QD quenching. We identify conditions for complete coupling without significant quenching, which are compatible with common QD polymer surfaces and various azide/alkyne pairs. Based on insight from the combinatorial screen and mechanistic studies of Cu coordination and quenching, we find that superstoichiometric concentrations of Cu can promote full coupling if accompanied by ligands that selectively compete the Cu from the QD surface but allow it to remain catalytically active. Applied to the conjugation of a K channel-specific peptidyl toxin to CdSe/ZnS QDs, we synthesize unquenched QD conjugates and image their specific and voltage-dependent affinity for K channels in live cells. We also report novel covalent protein labeling ligands (i.e., SNAP tags) that are specially optimized for use with inorganic nanocrystals.2 These synthetic hydrophilic benzylguanine ligands (i.e., SNAP tags) allow irreversible conjugation to SNAP tag proteins within live cells ~10-fold more efficiently than existing SNAP tags. This specific and improved protein labeling allows live-cell imaging of kinesin motors and dual-color QD labeling of kinesin heads and to track single protein stepping movement in live cells. 1. V.R. Mann, A.S. Powers, D.C. Tilley, J.T. Sack and B.E. Cohen. Azide-Alkyne Click Conjugation on Quantum Dots by Selective Copper Coordination. ACS Nano 12, 4469-4477 (2018) 2. S.M. Wichner, V.R. Mann, A.S. Powers, M.A. Segal, M. Mir, J.N. Bandaria, M.A. DeWitt, X. Darzacq, A. Yildiz and B.E. Cohen. Covalent Protein Labeling and Improved Single Molecule Optical Properties of Aqueous CdSe/CdS Quantum Dots. ACS Nano 11, 6773?6781 (2017)

Authors : Yujie Zhang1, Wubin Dai2, Yifeng Lei1*
Affiliations : 1 Department of Materials Engineering, School of Mechanical Engineering, Wuhan University, Wuhan 430072, China; 2 Department of Materials Science and Engineering, Wuhan Institute of Technology, Wuhan 430205, China

Resume : Introduction: Diabetes is a critical medical challenge affecting all of the world. The insulin injection according to the glucose level is a key issue for the treatment of type 1 and advanced type 2 diabetes. In this study, based on gold nanoclusters (GNCs) and MEMS microneedle patches, we aim to develop a smart insulin releasing system responding to the surrounding glucose levels. Method: We used GNCs as a novel carrier due to their high loading capacity of drugs (1). We decorated the GNCs with phenylboronic acid molecules, which serve as key switch factor for glucose-responsive insulin release. Moreover, using MEMS technology, we developed a microneedle patch containing the above GNCs for skin penetration and responsive drug release in vivo. Results: We are able to develop glucose-responsive insulin releasing GNCs, with strong sensitivity to glucose concentrations. Moreover, MEMS microneedle patches enabled the painless puncture of skins and the in vivo drug release. In both in vitro glucose solution and in type 1 diabetic mice in vivo, our system effectively released insulin according to the glucose concentrations, and can regulate the blood glucose in normoglycemic range for up to 3 days. Conclusion: This painless and responsive system can help the diagnosis and treatment of diabetes. Keywords: gold nanoclusters; microneedle patch; glucose control; drug delivery. References (1). Yifeng Lei, et al. Gold nanoclusters-assisted delivery of NGF siRNA for effective treatment of pancreatic cancer. Nature Communications. 2017; 8:15130.

Authors : Yutaro Hirai, Hiroshi Yabu
Affiliations : Tohoku University

Resume : Metal nanoparticle clusters are regarded as metamaterials, and dispersions of nanoparticle clusters are regarded as metafluids. Surface-enhanced Raman scattering (SERS) from molecules adsorbed on the nanoparticle clusters is one of a notable property of metafluids. SERS is expected to permit the realization of single-molecule detection in chemical and biological samples, especially cells and tissues. However, the most of SERS measurements have been done on substrates, local information of cells and tissues have been hard to obtain. In order to measure the local information of cells, using SERS active particles is one of the answers. To analyze biological samples using SERS, the SERS substrate should be excitable in the near-infrared (NIR) region to ensure high transparency in biological tissues. Furthermore, transporting the SERS particles to the desired position is crucial for obtaining high resolution. In this report, gold nanoparticle clusters based on polymer core?shell particles incorporating magnetic Fe3O4 nanoparticles were prepared via a self-assembly method. The enhancement factor of the SERS signal was determined by the size of composited gold nanoparticles. Furthermore, the migration direction of the gold nanoparticle cluster composite particles in aqueous media was successfully controlled by the application of an external magnetic field. This technique provides a novel way to analyze in situ distribution of biomolecules in cells and tissues.

Authors : Pedro M. Resende, Ruy Sanz, Olga Caballero-Calero, Marisol Martín-González
Affiliations : Instituto de Micro y Nanotecnología (IMN-CSIC), calle Isaac Newton 8, PTM, 28760 Madrid, Spain

Resume : The fabrication of flexible photonic materials with accessible and cost effective techniques has proven to be a difficult task in materials sciences, usually resorting to lithography techniques, opals and colloidal aggregates, greatly limiting the uses and sizes of these structures. New methods and structures for the production of Bragg refractors can be developed by taking examples available in the natural world, in which living organisms take advantage of the natural trade-off between employed resources and functionality to obtained efficient photonic structures that aid in several organic processes. This approach is made possible by the combination of a simple polymer infiltration technique, called melt infiltration, in periodically modulated aluminum oxide templates, producing a 3 dimensional polyethylene nanonetworks with a wide range of tuneable photonic responses. The reported method allows the production of such structures in wide areas, resorting to cheap materials like industrial grade polymers and aluminum alloys. The merging of an easy and scalable method with a 3 dimensional network-like structure offers new opportunities in areas as photonics, sensing, energy and clothing. [1] Resende, P. M. et al, Adv. Optical Mater. 2018, 1800408

10:15 Coffee break    
Nanostructured surfaces for tissue and cell control : Matthew R. Lockett
Authors : Prof. Paolo Netti
Affiliations : Interdisciplinary Research Centre for Biomaterials (CRIB); University of Naples Federico II and Centre for Advanced Biomaterials for Health Care; Istituto Italiano di Tecnologia, Napoli, Italy

Resume : In their native environment cells are constantly exposed to biochemical and biophysical signals that guide and regulate complex biological phenomena. Many of these signals impact on the adhesion properties of cells, which define morphology, cytoskeleton arrangements and cell mechanics. Adhesion signals are far from being static, but change in time and space according to specific programmes. Non-correct display of signals may result in catastrophic events. Yet, our understanding on the effects of the dynamics of signal presentation on cell functions and fates is limited. Here we present our recent developments in the engineering of light-responsive platforms to enable the dynamic presentation of patterns of adhesion signals whose features can be controlled in space and time. Irradiation of azobenzene based substrates can alter surface topography in the time frame of few tens of seconds, allowing formation of submicron features, a scale that interferes with focal adhesion formation. We show the potency of these substrates in stimulating individual cells with topographic patterns over varying lengths and timescales, and how dynamic patterns alter cytoskeleton arrangements and cell mechanics. Development of platforms for dynamic signal display would provide valuable insights into cell-biophysical signal interactions and into mechanotransduction phenomena, paving the way to novel systems that mimic physiologic or pathologic extracellular environments for in vitro cell stimulation.

Authors : G. Sarau1,2, P. Milovanovic3,4, A. vom Scheidt3, E. ?. Zimmermann3, K. Mletzko3, K. Püschel5, Marija Djuric4, B. Hoffmann2, T. Yorgan3, M. Schweizer6, M. Amling3, B. Busse3,7 and S. Christiansen1,2,
Affiliations : 1. Helmholtz-Zentrum Berlin für Materialien und Energie GmbH, Hahn-Meitner-Platz 1, 14109 Berlin, Germany; 2. Max Planck Institute for the Science of Light, Staudtstr. 2, 91058 Erlangen, Germany; 3. Department of Osteology and Biomechanics, University Medical Center Hamburg-Eppendorf, Lottestrasse 55a, 22529 Hamburg, Germany; 4. Laboratory for Anthropology and Skeletal Biology, Institute of Anatomy, Faculty of Medicine, University of Belgrade, Dr Subotica 4/2, 11000 Belgrade, Serbia; 5. Department of Forensic Medicine, University Medical Center Hamburg-Eppendorf, Martinistr. 52, 20246 Hamburg, Germany; 6. Center of Molecular Neurobiology, University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany; 7. Materials Sciences Division, Lawrence Berkeley National Laboratory / University of California-Berkeley, CA 94720, USA; 8. Physics Department, Freie Universität Berlin, Arnimallee 14, 14195 Berlin, Germany

Resume : The detailed understanding of interfaces in biological systems is essential to achieve controllable bioresponses. Here, we characterized two types of biointerfaces in human cortical bone tissues with osteoporosis using high-resolution microscopy and spectroscopy techniques and proposed novel strategies for improving their biomechanical response. First, the boundary between osteonal and interstitial bone materials known as the cement line (CL) was investigated. It was found that CLs are hypermineralized (tougher) interfaces with varying mineralization levels depending on the osteon age, indicating distinct biomineralization dynamics in CLs and osteons attributed to their different organic compositions. According to finite element modelling, having CLs with higher toughness deflect microcracks, thus preventing extensive bone fracture. Second, the interfacial interaction between osteocyte cells and surrounding bone tissue was studied. Highly mineralized plugs explained by a unique biomineralization mechanism following osteocytes death were found. These occlusions can locally alter cellular communication and bone homeostasis, thus decreasing bone fracture resistance. Future medication has to focus on preserving osteocytes, also because they can inhibit mineralization resulting in an empty pericellular space crucial for the fluid flow between cells. Based on these results, smart bioinspired implant materials can be developed to ensure bone stability in elderly individuals.

Authors : Jorge Morgado1,2, Laura Sordini1,3, Fábio F. F. Garrudo1,3, Carlos A. V. Rodrigues2,3, Frederico C. Ferreira2,3
Affiliations : 1. Instituto de Telecomunicações, Av. Rovisco Pais, 1049-001 Lisboa, Portugal; 2. Department of Bioengineering, Instituto Superior Técnico, University of Lisbon, Portugal; 3. iBB-Institute for Bioengineering and Biosciences, Instituto Superior Técnico, University of Lisbon, Av. Rovisco Pais, 1049-001 Lisboa, Portugal

Resume : Stem cell culture is of paramount importance in tissue engineering and regenerative medicine. Neural stem cells or mesenchymal stem cells therapies have the potential to treat neurodegenerative diseases, either by replenishing the cell pool or through the secretion of paracrine factors. In order to successful apply these therapies, we need to develop appropriate scaffolds that, by mimicking the extracellular matrix to culture cells in vitro and control their fate, offers the prospects to turn these in vitro studies into efficient medical processes. We have been studying the use of conjugated polymers substrates for neural stem cells cultivation and/or differentiation using patterned devices [1]. In addition to the thin film-based scaffolds, the use of polymeric fibers, prepared by electrospinning, based on various polymers, including blends with conjugated polymers, is also being explored. In this communication we report on our progress in the search for polymer based films and fibers scaffolds, including the use of conductive polymers as these offer the possibility to use electrical stimuli, and their ability to sustain viable cell culture. We acknowledge FCT financial support under the projects NEURON (PTDC/CTM?CTM/30237/2017) and UID/EEA/50008/2013. [1] F. Pires, Q. Ferreira, C. A. V. Rodrigues, J. Morgado, F. C. Ferreira, Biochimica et Biophysica Acta General Subjects, 1850, 1158-1168 (2015).

Authors : Guillaume Le Saux, ?? Netanel Bar?Hanin, ?? Avishay Edri, § Uzi Hadad, ? Angel Porgador, § Mark Schvartzman??
Affiliations : ?Department of Materials Engineering, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; ?Ilse Katz Institute for Nanoscale Science & Technology, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel; §The Shraga Segal Department of Microbiology, Immunology and Genetics, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, 84105, Israel

Resume : Cells sense their environment by transducing mechanical stimuli into biochemical signals. Commonly used tools to study cell mechanosensing provide limited spatial and force resolution. Here, a novel nanowire?based platform for monitoring cell forces is reported. Nanowires are functionalized with ligands for cell immunoreceptors, and they are used to explore the mechanosensitivity of natural killer (NK) cells. In particular, it is found that NK cells apply centripetal forces to nanowires, and that the nanowires stimulate cell contraction. Based on the nanowire deformation, it is calculated that cells apply forces of down to 10 pN, which is the smallest value demonstrated so far by microstructured platforms for cell spreading. Furthermore, the roles of: i) nanowire topography and ii) activating ligands in the cell immune function are studied and it is found that only their combination produces enhanced population of activated NK cells. Thus, a mechanosensing mechanism of NK cells is proposed, by which they integrate biochemical and mechanical stimuli into a decision?making machinery analogous to the AND logic gate, whose output is the immune activation. This work reveals unprecedented mechanical aspects of NK cell immune function and introduces an innovative nanomaterial for studying cellular mechanics with unparalleled spatial and mechanical resolution.

Authors : Nien-Chen Tsai1+, Jia-Wei She2+, Jhih-Guang Wu2, Peilin Chen3, Yu-Sheng Hsiao4*, and Jiashing Yu1*
Affiliations : 1. Department of Chemical Engineering, National Taiwan University, Da-an, Taipei City 10617, Taiwan. 2. Department of Materials Science and Engineering, National Taiwan University, Da-an, Taipei City 10617, Taiwan. 3. Research Center for Applied Sciences, Academia Sinica, 128 Sec. 2, Academia Rd., Nankang, Taipei City, 11529, Taiwan. 4. Department of Materials Engineering, Ming Chi University of Technology, Taishan, New Taipei City 24301, Taiwan.

Resume : Controlled extracellular chemical and topographical cues can generate physicochemical changes that influence the proliferation and differentiation of neural cells; external electrical stimulation (ES) via conductive bioelectrodes can promote neural differentiation by increasing neurite outgrowth. Because rat pheochromocytoma (PC12) cells tend to differentiate into neuron-like cells upon treatment with nerve growth factor (NGF), we used PC12 as a model to explore the possibility of using a well-designed poly(ethylene oxide) (PEO)/poly(3,4-ethylenedioxythiophene):polystyrenesulfonate (PEDOT:PSS) blend solution to fabricate functional bioelectrodes presenting biological fouling/antifouling surfaces, thereby regulating the cell adhesion, proliferation, and differentiation properties. In this study, we found that a flat PEO/PEDOT:PSS composite film, fabricated through spin-coating, operated through a contact repulsion mechanism that limited cell attachment and proliferation; in contrast, the aligned and random PEDOT:PSS nanofibers fabricated through electrospinning promoted neuron adhesion efficiently and allowed manipulation of the cell morphology. Furthermore, we performed ES of PC12 cells to investigate the influence of the conductive random and aligned PEO/PEDOT:PSS composite nanofiber mats on the enhancement of neurite outgrowth, as well as the relative gene expression of Nestin, Tuj1, and MAP2. The PC12 cells on the aligned topography displayed predominantly bipolar neurites along the direction of the nanofibers; PC12 cells on the random nanofibers produced a greater number of neurites than did those on the aligned nanofibers; the neurite length and neuronal gene expression level were enhanced by greater than 60% relative to those of control tissue culture polystyrene plate (TCPS) substrates under ES. Therefore, combining this unique PEDOT:PSS blend solution with various fabrication processes appears to be a facile approach toward bioelectronic interface coatings displaying tunable surface properties for manipulating the cellular behavior of neurons during ES.

12:00 Lunch    
Biofilms : Paolo Netti
Authors : Henk J. Busscher
Affiliations : University of Groningen and University Medical Center Groningen Antonius Deusinglaan 1, 9713AV Groningen, The Netherlands

Resume : Nanostructured surfaces are called “promising” to control bacterial adhesion and biofilm formation. Initial adhesion is followed by emergence of surface-programmed bacterial properties and biofilm growth. A distinction between nanostructured surfaces can be made based on periodic- or random-occurrence of features, although often nanostructured surfaces are microstructured due to merging of their nanofeatures. Characterization of such surfaces is not trivial due to the myriad of different nanoscaled morphologies. Both superhydrophobic and hydrophilic, nanostructured surfaces generally yield low bacterial adhesion. On smooth surfaces, bacteria deform when adhering, causing membrane surface tension changes and responses yielding emergent properties. Adhesion to nanostructured surfaces, causes multiple cell wall deformation sites when adhering in valleys, while for hill-top adhesion, highly localized cell wall deformation occurs. Accordingly, adhesion to nanostructured surfaces yields emergent responses ranging from pressure-induced EPS production to cell wall rupture and death. Other promising features are increased antibiotic housing, thermal effects and photo-induced ROS production, but the latter two promises are based on properties of suspended nanoparticles and may not hold in nanostructured coatings or materials. To bring nanostructured coatings and materials to application, experiments are needed that go beyond the current limit of the laboratory bench.

Authors : Stephanie Fulaz, Caio Barros, Henry Devlin, Dishon Hiebner, Laura Quinn, Stefania Vitale, Eoin Casey
Affiliations : UCD School of Chemical and Bioprocess Engineering, University College Dublin, Belfield, Dublin 4, Ireland

Resume : In nature bacteria generally exist as biofilms. Biofilms are a dynamic and structurally complex community of microorganisms embedded in a self-produced matrix of extracellular polymeric substances (EPS). One possible approach to eradicate unwanted biofilms is to use smart responsive technologies that are activated by an environmental cue. Due to bacterial metabolism, cells embedded in the biofilm create a localized acidic microenvironment which is unaffected by the external pH. Therefore, pH monitoring is a promising approach for understanding the complexities of biofilms with potential applications in diagnostics; however, pH measurement is not a trivial task in a 3D and highly heterogeneous system such as a biofilm. A nanoscale pH-responsive sensor would enable in-situ analysis of pH gradient inside biofilms, without altering its natural structure. Based on this, a pH sensor was designed by synthesising mesoporous silica nanoparticles (47±4 nm diameter) conjugated to a pH-sensitive dye (fluorescein-F) and a pH insensitive dye (rhodamine-R) as an internal standard. The fluorescence intensity (IF) drops drastically when the pH is decreased from 8 to 3.5, the fluorescence intensity (IR) was approximately constant. The ratio IF/IR is a sigmoidal curve with respect to the pH, with a working pH range between 4 and 7. The synthesised pH-responsive particles allowed for an accurate measurement of the extracellular pH inside the biofilm matrix, and through confocal microscopy, the biofilm pH can be mapped.

Authors : Yajuan Zou, *Naoki Komatsu
Affiliations : Graduate School of Human and Environmental Studies, Kyoto University

Resume : In biological fluids, proteins are adsorbed onto the surface of nanoparticles (NPs) to form a coating known as protein corona. Most of the corona proteins act as opsonin which activates the macrophage from immune system to uptake NPs, leading to the rapid removal of NPs1). This restricts the development of nanomedicine. Although conjugation with linear polyethylene glycol (PEG) is the standard approach to reduce protein attachment and to avoid non-specific uptake, it cannot fully prevent the opsonization. On the other hand, we have demonstrated polyglycerol (PG) as a promising alternative to PEG, because PG enhanced the aqueous dispersibility and gave stealth effect to NPs2). In order to understand the role of PG, we compare protein affinity and stealth effect of PG and PEG grafted nanodiamond (ND-PG and ND-PEG, respectively) with different density in this paper. Protein analyses by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) indicated that PG was much more resistant than PEG to adsorption of the opsonin proteins such as IgG and complement protein. In particular, there was almost no protein on the dense PG layer. In vitro stealth effect was revealed by TEM; almost no ND-PG was observed in the TEM images of U937 macrophage, while there was ND-PEG in the macrophage. This indicates that PG has much better stealth effect than PEG. In vivo stealth effects including blood circulation and biodistribution will be reported in due course. References: 1) S. Schöttler et al., Nat. Nanotechnol., 2016; 2) L. Zhao, N. Komatsu et al., Angew. Chem. Int. Ed. 2011

Authors : Patrick Lemoine*1, Chris Dooley1, Emma Harrison2, Dorian Dixon1
Affiliations : 1,NIBEC, Ulster University, Shore Road, Newtownabbey, BT37 0QB, UK 2, Terumo BCT- Ltd, Old Belfast Road, Millbrook, Larne BT40 2SH, UK

Resume : Nano-particles can be used as drug delivery systems to target drug action on specific organs of the body, hence reduce dosage and side effects. One example is the co-functionalization of gold nano-particles (AuNP) with PEG to enhance dispersion and with peptides, to increase cellular uptake [1]. Yet, it is difficult to optimize both functions simultaneously. Varying the PEG end-groups, two methods have been considered, often termed the mixed monolayer and linker (i.e. head-to-tail) approaches, although in both cases, the precise arrangements of the grafted PEG and peptide ligands on the AuNP surface remain unknown. This issue is examined here principally using AFM microscopy. Firstly, AuNP were functionalized separately with PEG and peptide ligands to gauge the affinity of the ligands to the gold nanoparticles. Ligand adsorption experiments were also conducted on gold films, which have shown to be good model systems for AuNP [2-6]. AFM microscopy of the AuNP shows that the ligands improve dispersion and modify the tip/surface adhesion behaviour on the nanoparticles. For the gold films, macro-level sessile drop measurements indicate that PEG and peptide ligands exhibit similar affinity to the gold surface. However, at the nano-level, AFM experiments show differences in the morphology, continuity, thickness and cohesion of adsorbed ligand films. Differences in tip/surface adhesion in water are also measured. Preliminary experiments on co-functionalization using the mixed monolayer and linker approaches indicate differences in AuNP diameters for the two methods. Overall, this study demonstrates that AFM microscopy is a useful tool for investigating the interaction between biological ligands and AuNP. 1. Harrison E. et al, Nanomedicine 11(7): 851-865, 2016 2. Fenter P. et al, J. Chem. Phys. 106.4: 1600-1608 (1997 3. Luedtke, WD et al, J. Phys. Chem. 100.32: 13323-13329 (1996) 4. Pradeep, T. et al, Pure Appl. Chem. 74.9: 1593-1607 (2002) 5. Vericat, C. et al. J. Phys: Cond. Matter 20:18, (2008) 6. Wang, Z. L. et al, Surf. Sci. 440.1: 809-814, (1999)

Authors : Stefania Vitale, Caio H. N. Barros, Henry Devlin, Stephanie Fulaz Silva, Dishon W. Hiebner, Laura Quinn, Eoin Casey
Affiliations : University College Dublin, School of Chemical and Bioprocess Engineering, Belfield, Dublin 4 (Ireland)

Resume : Nanoparticles (NPs) have been shown to possess antibacterial properties and are considered a promising tool for biofilm control. Many studies indicate that NPs mainly interfere with the bacterial metabolism and cellular membranes; however fundamental understanding is still lacking on the exact mechanisms involved in these actions, namely with regards to the role of the biofilm self-produced extracellular polymeric matrix (EPS). This work deals with the use of engineered silica NPs to elucidate the role of the EPS in NPs-biofilm interactions, with a main focus on how NPs features (charge, size and hydrophobicity) combine with those of the EPS (composition, density and structure) to determine NPs transport, uptake and accumulation within the biofilm. Engineered fluorescent silica NPs were prepared and their surface functionalised to tailor charge and hydrophobicity (modification with epoxide and amine groups, PEG, benzoic acid and alkyl silanes). Biofilms grown from two Pseudomonas strains were exposed to the NPs and their interaction with the EPS was assessed through confocal microscopy, UV-Vis, IR and fluorescent spectroscopy, dynamic light scattering, Z-potential analysis. Significant differences are observed in uptake and distribution as a function of NP charge and surface groups, suggesting selective NP-EPS components interactions. The outcome of this study will be useful in applications where antibiofouling technology is needed (eg. water, food and biomedical industries).

Authors : Babak Mehrjou (1), Mo Shi (1), Guomin Wang (1), Abdul Mateen Qasim (1), Hao Song (2), Kaifu Huo (2), Paul k. Chu (1),*
Affiliations : (1) Department of Physics and Materials Science, City University of Hong Kong, Tat Chee Avenue, Kowloon, Hong Kong, China (2) Wuhan National Laboratories for Optoelectronics, School of Optical and Electronic Information, Huazhong University of Science and Technology, Wuhan 430074, China

Resume : Bacteria attachment and growth on implants can cause serious problems and even death to patient. Most materials have been using for bone implants are metallic ones which will be remained in the body for whole life and if it will be infected by any reason, it should be removed immediately. Therefore, scientists have been focused on more natural and biodegradable materials and silk can be a prominent one because of its unique properties like excellent strength, biodegradability and biocompatibility. A new strategy to kill and prevent bacteria from adherence to the implant is introducing nano topography on the surface of implant because the stress at the contact area of bacteria cell wall will be increased significantly. By introducing nano topography to the surface of materials usually the water contact angle has been increased and the surface becomes superhydrophobic. Superhydrophobicity can help to reduce bacteria attachment but at the same time cell proliferation is also prevented. To achieve a good combination of antifouling and cell proliferation, hydrophilic nanopatterned silk-based material is fabricated by oxygen plasma etching method. The fabricated cones height are about 400 nm and center-to-center distance between two cones are about 300 nm. Bacteria culturing experiments showed more than 90% reduction in attachment of bacteria (both S.aureus and E.coli) to the surface while the water contact angle after plasma treatment is about less than 20 degree.

Poster Session II : TBD
Authors : N. L. Costa; T. Flinois; M. Cronier; E. Lebègue; F. Barrière
Affiliations : Univ Rennes, CNRS, Institut des Sciences Chimiques de Rennes - F-35000 Rennes, France

Resume : Changes in the pH of biological systems are crucial to maintain their properties. In microbial fuel cells (MFCs), anode respiring bacteria like Geobacter sulfurreducens can form biofilms that are able to oxidize organic matter to CO2 while transfer electrons to electrode. Conversely, protons are also produced and released to the medium leading to the biofilm acidification. This changes on local pH usually leads to alterations on the bioenergetics process of microbial communities and hence on MFCs’ performances. It is therefore interesting to measure the interfacial pH and its evolution during or after biofilm metabolism of organic substrates. Covalent grafted quinones like catechols can be used as probes to measure and evaluate the interfacial pH during biofilm formation onto carbon electrodes. For monitoring pH variations induce by ionophores in subcellular scale, 5-aminosalicylic acid (5ASA) has been used to form redox active film onto glassy carbon electrode surface through recurrent cyclic voltammetry. The variation of the apparent standard potential of the 5ASA-based film as a function of pH is linear over the entire studied pH range (pH 2 to 10) with a slope of -79 mV per pH unit. Upon deposition of 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC) onto the modified electrode, ionophores such as valinomycin and nigericin were incorporated into the lipid deposit in order to probe pH at the modified electrode/lipid deposit interface.

Authors : Mustafa Kansiz1*, Eoghan Dillon1; and Isao Noda2,3
Affiliations : 1 Photothermal Spectroscopy Corp, Santa Barbara, CA 93101, U.S.A. 2 Department of Materials Science and Engineering, University of Delaware, Newark, DE 19716, U.S.A. 3 Danimer Scientific, Bainbridge, GA 39817, U.S.A. Keywords: IRaman, Simultaneous IR & Raman, Instrumentation development, optical photothermal spectroscopy, 2D-COS, bioplastics

Resume : Optical Photothermal Infrared (O-PTIR) is an emerging IR spectroscopy technique requiring no contact with the sample (Figure 1) and providing for highly spatially resolved infrared hyperspectral images down to the 500 nm level. Recent advances have also now made possible the simultaneous measurement of position co-registered Raman spectra - IRaman. This range of spatial resolution is especially suited for the analysis of practically important industrial multicomponent and multiphase product samples, including composites and laminates comprising bioplastics (Figure 2). Such systems are expected to exhibit different degrees of mixing and spatial segregation of individual constituents, which in turn strongly affect the end use performance of the material. In this study, hyperspectral IR (O-PTIR) and Raman image data was obtained simultaneously using the mIRage IR microscope, for a bioplastic composite system is subjected to various forms of two-dimensional correlation spectroscopy (2D-COS) analysis to extract pertinent information about compositional distribution and possible molecular level interaction among the constituents. This first-of-a-kind capability, provides for simultaneous IR and Raman spectra from the same spot at the same time with the same spatial resolution, whilst both data channels (IR & Raman) being spatially registered. This approach takes full advantage of spectral complementarity of IR and Raman to provide for a more thorough sample characterisation. Furthermore, by taking advantage of the simultaneous measurement of IR and Raman spectra using mIRage system, it becomes possible to carry out the 2D hetero-spectral correlation of spectral images, providing for new insights, by utilising the full complementarity of IR and Raman data.

Authors : Teng Zan,Xiaoyan Yi,Chen Lin,Junnan Zhou,Junxi Wang,Jinmin Li
Affiliations : Research and Development Center for Solid State Lighting, Institute of Semiconductors, Chinese Academy of Sciences

Resume : The rapid rise of optogenetics in neuroscience research over the past decade has led to signifcant advancements in animal studies, medical research and disease treatment. Recent efforts have been focused on flexible, wireless powered, miniaturized optogenetic devices. Here, we report a new optogenetic system which consists of wireless controllable drive module and injectable probe. The system can be applied in multiple animal model (e.g., mouse, monkeys and flies) and different fields of neuroscience(e.g., fundamental research on neural circuit, neurotherapeutics for Parkinson’s disease, drepression, anxiety, cognitive disorders and epilepsy). The system adopts bluetooth 4.0 wireless communication protocol, and the device can be controlled remotely by a terminal(e.g., smart phone, tablet or computer) with a distance as far as 50 meters. Besides, frequency and power of light from the μ-LEDs are adjustable as well. In order to obtain movement of measured object, the drive circuit of the device is equipped with built-in motion sensor modules and power management module, they are energized by a rechargeable lithium battery which has 10-hours battery life. In addition to the device mentioned in this article, we are also trying to fabricate a smaller miniature chip-level optogenetic device which is made from semiconductor technologies entirely and has a anticipated size of 16mm2. In the future work, the optimized coil design for reducing the size of the devices, flexible substrate and high-performance light sources which include better monochromaticity and less divergence angle will be taken into account as well.

Authors : Monika Lelonek, Dr. Petra Goering
Affiliations : SmartMembranes GmbH, Halle, Germany

Resume : Nano porous anodic alumina structures is a widely studied material that is used for corrosion protection of aluminum surfaces or as dielectric material in microelectronics applications. For more than 40 years porous alumina has been the subject of investigations. It exhibits a homogeneous morphology of parallel pores which grow perpendicular to the surface with a narrow distribution of diameters and interpore spacings, the size of which can easily be controlled between 15 and 400 nm. Monodomain porous alumina templates with very high aspect ratios can also be synthesized by using lithographic preparation. The combination of self-assembly and lithography allows the preparation of porous alumina templates with various configurations of pore arrangement that are not accessible by other state-of-the-art methods. Macro porous silicon structures, prepared by an photo-electrochemical process, has also gained interest in research for many applications which have a demand for mechanical and chemical stability as well as a high order of the pores. The pore diameters at SmartMembranes can differ from 800 nm up to 17 µm using lithographic pre-structuring (up to 100 µm possible). The standard deviation of pore diameter and interpore distance is lower than 10 %. Because of the lithographic pre-structuring technique macro porous silicon with its high ordered structure represents an ideal 2-D photonic crystal (PC) exhibiting novel properties for the propagation of infrared light within the pores. Because of the above mentioned unique properties, nano porous alumina and macro porous silicon can be used in a wide range of applications, such as filters, as platforms for muliti-functional sensors (lab-on-the-chip), as antimicrobial structure, and especially as templates for the fabrication of nanometer-scale bio composites, such as nanotubes or nanowires by using polymer melts for biomimetic applications. One of the joint innovative developments at SmartMembranes is the multifunctional biochip sensor based on the macro porous silicon membranes (in collaboration with ANGLE Biosciences Inc.). This flow-through chip is based on a lab diagnostic method for the determination of DNA and protein species. In this case, complex elaboration methods are replaced by substance-selective separations in the pores of the membrane (transition from 2D to 3D structures with defined surface modification of the inner pore walls). The single-use consumable has been designed for routine and focused multiplex analysis for nucleic acids or proteins. The biochip is a disposable device consisting of a 6.5 mm square chip mounted on a plastic tube. The chip is made of porous silicon with > 200.000 micro channels incorporated in that area. A single capture probe site occupies approximately 70 macro pores. This approach facilitates the interaction between target molecules and immobilized probes, resulting in 3 to 4 times faster hybridization of oligonucleotides or protein binding. A highly selective multifunctional biosensor system could be realized by using a electro-sensory measurement technology. Nano porous alumina membranes with higher aspect ratios can also be implemented in flow-through devices, e.g. filtration modules for sterile filtration of liquids and gases or for the separation of viruses with an exact cut-off. They are also used for cultivation of cells due to their good biocompatibility characteristics. Since the membranes are transparent when wet, they are highly suitable for microscopic investigations or to monitor cell-cell-interactions. Novel trend also show the usage of nano porous alumina as flow control for drug delivery systems, where as the fluidics can be exactly calculated due to the high order and precise sizes of the pores offering flow control depending on pore size.

Authors : Hsin-Ning Ku, Tri-Rung Yew*
Affiliations : Department of Materials Science and Engineering, National Tsing Hua University, Hsinchu, Taiwan 30013

Resume : Metal oxide materials have drawn much attention in the application of biosensors recently. Various metal oxide materials such as indium tin oxide (ITO), zinc oxide (ZnO) and titanium dioxide (TiO2) with different surface strategies have been utilized in the versatile biosensors to improve the detection performance. In this work, thermal vapor deposition was used to deposit Tin-based oxide thin films as biosensor electrodes with different molar ratio and ceramic processing conditions. After preparation, the morphology and the elements ratio of thin films were characterized by scanning electron microscopy (SEM) and energy dispersive X-ray spectrometry (EDX), respectively. The electrical properties were analyzed by electrochemical impedance spectroscopy (EIS) analysis and Cyclic-Voltammetry (CV) analysis. It is expected the novel tin-based oxide will manifest the potential in the application of biosensors.

Authors : Laura Ferlauto, Paola Vagni, Elodie Geneviève Zollinger, Sara Pagnamenta, Diego Ghezzi
Affiliations : Medtronic Chair in Neuroengineering, Center for Neuroprosthetics and Institute of Bioengineering, School of Engineering, École Polytechnique Fédérale de Lausanne, Switzerland

Resume : The research on transient technologies for biomedical applications focuses on the development of devices able to disappear in the biological environment after a fixed time, thus cancelling the risks related to surgical retrieval [1]. Despite astonishing progress in the field [2], one of the main issue still to overcome is the short functional lifetime of transient recording/stimulating devices in the body, which is typically a few days. In the perspective of extending their duration, and consequently their possible applications, our strategy is to abandon the silicon-based approach so far implemented and to rely on entirely polymer-based devices. For this purpose, we fabricated probes for neural signal recording based on Polycaprolactone as support and encapsulation and Poly(3,4-ethylenedioxythiophene)-poly(styrenesulfonate) as conductive component. In-vitro electrochemical ageing tests (NaCl, 37 °C) were performed to estimate the devices functionality in an environment similar to the biological one, whereas the materials degradation and the foreign-body response were monitored at different time-points (3, 9 and 12 months) after implantation in mice brains (visual cortex area). Chronic recordings of visually evoked potentials up to several weeks finally demonstrated the in-vivo functional durability of the devices. This work was supported by European Commission (project № 701632). [1] Kang S.-K. et al., Nature 530, 2016; [2] Koo J. et al., Nat. Med. 24, 2018.

Authors : Po-Chun Chen (1), Fu-Erh Chan (1), Zheng-Ting Tang (2), You-Yin Chen (3), Wei-Chen Huang (2), Shao-Sian Li (2), Jiashing Yu(4).
Affiliations : 1 Department of Materials Mineral Resources Engineering, National Taipei University of Technology 2 Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University 3 Department of Biomedical Engineering, National Yang-Ming University 4 Department of Chemical Engineering, National Taiwan University

Resume : Implantable neurostimulation devices have been attracted considerable attention recently. When a neural probe is implanted in vivo, neural disordered disease can be treated by electrostimulation. Additionally, electrically controlled drug release has been particularly attractive for bioelectronics because the electrical signal is portable and controllable on-demand, without the requirement of large or special equipment. However, protein-based bioactives such as growth factors or antibodies are easily denatured to lose their bioactivity in response to external stimulation. It is challenging to develop a bioelectrode system that permits the electrically responsive release of proteins without damage. In this study, a polyimide-based biocompatible microelectrode array has been treated by a facile co-electrodeposition method to form hybrid film of iridium oxide and plasma protein. We carried out a cyclic voltammetry approach to co-electrodeposit iridium oxide and plasma protein on Au microelectrode array. We characterized and evaluated the hybrid electrolytes and deposited films for bio-electrode applications. We also demonstrated the releasing behavior triggered by an electric field. In addition, the biocompatibility of the hybrid films was also investigated by testing the cell viability.

Authors : Jaehyun Kang1, Yong Tae Kim2, Junhyoung Ahn3, Seok Jae Lee2, Jaejong Lee3, and Ki-Bum Kim1
Affiliations : 1 Department of Materials Science and Engineering, Seoul National University, 599 Gwanak-ro, Gwanak-gu, Seoul 08826, Korea 2 National Nanofab Center (NNFC) 335 Gwahakno, Yuseong-gu, Daejeon 305-806, Korea 3 Korea Institute of Machinery and Materials, 156 Gajeongbuk-ro, Yuseong-gu, Daejeon 305-343, Korea

Resume : Isolation, purification and concentration of nucleic acids such as DNA and RNA are essential skills in various biotechnology. Because the sample pretreatment results can affect the downstream process, effective and fast sample pretreatment technology has been required. Nucleic acid isolation, purification and concentration methods have evolved over the past several decades. A nucleic acid extraction method widely used in the past is a process using a silica membrane or a magnetic bead. Conventional methods are time consuming and results vary depending on the user's proficiency. In addition, extraction of short nucleic acids such as microRNAs by a conventional method has the disadvantage of low efficiency and high cost. Therefore, the need for rapid, efficient and inexpensive isolation, purification and concentration of nucleic acids has increased in technologies such as molecular diagnostics and pathogen detection. There are several issues in the process of isolation, purification and concentration of nucleic acids, one of which is effective cell lysis. There are two ways to disrupt a cell: physical or chemical. Physical methods include bead beating and sonication, and chemical methods include cell lysis using a surfactant. The second is purification. When the ratio of the absorbance of light in the 260nm and 280nm ranges is measured, it is considered a pure nucleic acid when the DNA has a value of 1.8 and the RNA has a value of about 2.0. The third is concentration, which previously required the use of an ultracentrifuge method, such as density gradient separation, which is expensive and time-consuming to concentrate the sample. Here, we demonstrate a technique for selectively separating nucleic acids with high surface charge relative to their mass in an aqueous solution by electrophoresis method using multi-nanopore structure made of widely used conventional semiconductor processes.

Authors : L.A. Osminkina 1,2, M.B. Gongalsky 1, U.A. Natashina 1, G.Z. Gvindzhilia 1, A.P. Sviridov 1, S.N. Agafilushkina 1, K. P. Tamarov 1, A. A. Kudryavtsev 3
Affiliations : 1 Lomonosov Moscow State University, Department of Physics, Leninskie Gory 1, 119991 Moscow, Russian Federation; 2Institute for Biological Instrumentation of Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russian Federation 3Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Pushchino 142290, Russian Federation

Resume : We report usage of porous silicon nanoparticles (PSi NPs) for theranostics, which means simultaneous diagnostics and therapy by the same active agent. Efficient PL properties of PSi NPs allow fluorescent staining of cells in optical bioimaging. We also performed multi-modal visualization of PSi NPs using linear and non-linear optical imaging techniques such as confocal microscopy, Raman and coherent anti-Stokes Raman spectroscopy. PSi NPs penetrated into the living cells via endocytosis mechanism without any substantial toxicity in concentrations up to 0.5 mg/ml, and completely dissolved after two weeks of the incubation, which was revealed by Raman scattering from the nanoparticles inside the cells. At the same time, PSi NPs delivered chemotherapeutical drugs into the cells and also acted as sensitizers of visible and infrared light, ultrasound and radio waves, which resulted in destruction of the cancer cells. This work was supported by the Russian Science Foundation (Grant ? 17-12-01386).

Authors : Jiyeon Lee, Oh Seok Kwon*
Affiliations : Infectious Disease Research Center, Korea Research Institute of Bioscience & Biotechnology (KRIBB)

Resume : In this study, ultrasensitive and precise detection of a representative brain hormone, dopamine chased and demonstrated using functional synthesis by polypyrrole nanotubes modified with aptamer. The produced aptasensor was composed of a micropatterned gold electrode on the glass, polypyrrole nanotube with carboxylated , and specific aptamer molecules. The sensor was constructed by sequential deposition of the PPy-COOH nanotubes and aptamer molecules on the electrode. The sensitivity and selectivity of this sensor were monitored using field effect transistor type measurements. In addition, real dopamine released from PC12 and SH-SY5Y cells induced by high concentration potassium ion (K ) stimulus were also analyzed and compared with the data obtained from the sensitivity (1 nM) and selectivity tests. This article can provide the feasibility for practical use of simple and efficient field effect transistor type aptasensor.

Authors : Pedro M. Resende, Cristina V. Manzano, Marisol Martín-González
Affiliations : Instituto de Micro y Nanotecnología (IMN-CSIC), calle Isaac Newton 8, PTM, 28760 Madrid, Spain

Resume : Hierarchical structures can be found throughout multiple examples in the natural world, conferring better properties to biological systems, like the enhanced photonic response in Morpho butterfly wings or the increased adhesion of suction cups in Octopi. In this work we follow a bioinspired approach in order to fabricate a hierarchical nanostructured polymer film resembling the octopus’ suction cups through a simple patterning method. The patterning is based on the combination of porous alumina templates, a well-known self-ordered system that produces an array of hexagonally packed nanopores, and the melt infiltration of a conductive polymer, PEDOT-PSS, yielding a patterned conductive film. A study is presented of the different properties and morphology of these films. [1] Resende, P. M. et al, Adv. Optical Mater. 2018, 1800408 [2] Baik, S. et al, Adv. Sci. 2018, 5, 1800100

Authors : Sen Mei1, Mingyi Wang2, Juan Yang1, Paul Hoff Backe2, Brian Wabende1, Mathieu Grandcolas1, Magnar Bjørås2, Christian Simon1
Affiliations : 1. SINTEF Industry, Department of Materials and Nanotechnology, P.O. Box 124 Blindern, NO-0314 Oslo, Norway; 2. Department of Microbiology, Oslo University Hospital, P.O. Box 4950 Nydalen, NO-0424 Oslo, Norway

Resume : Recently, the direct conversion of the waste CO2 emission as feedstock into valuable chemicals has attracted increasing research interest world widely. A number of approaches such as chemical, electrochemical, photochemical or biological routes have used CO2 as a sustainable carbon resource for the production of chemicals. In our work, a novel hybrid photoelectrochemical cell by using formate dehydrogenase (FDH) as biocatalyst was applied, to convert CO2 into energy-rich compounds. Therefore, it becomes imperative to immobilise FDH onto the surface of cathode with high electron transfer efficiency. In this work, several metallic substrates and carbon-based materials, such as carbon nanotube and graphene coating, were selected as electrodes to immobilise FDH enzyme onto their surfaces. In order to achieve an efficient immobilization, both chemical and physical functionalization were applied to the selected surfaces. A fast antibody-based dot blot method was established to detect the efficiency of the immobilization of the proteins. The activity of the purified enzymes was investigated by measuring the conversion ratio of NADH to NAD+. Preliminary results showed that the attachment of enzymes strongly depends on surface treatment of the electrodes. The immobilization of the enzymes was significantly improved by forming chemical bonding between the enzyme and the carbon-based materials. The electron transport and activity of the enzyme on the electrode surface will be investigated. Acknowledgements This project has received funding from Research Council of Norway (under the NANO2021 programme), project CO2BioPEC (250261).

Authors : Haoran Sun, Min Wang *
Affiliations : Department of Mechanical Engineering, The University of Hong Kong, Pokfulam Road, Hong Kong * Email:

Resume : Bicontinuous interfacially jammed emulsion gels (?bijels?) and bijels-derived structures may find many applications. But their wide application is hindered by difficulties in bijels fabrication. Bicontinuous bijels-derived structures possess interconnected channels that are favored in tissue engineering applications as the channels can facilitate transportation of nutrients, oxygen and bioactive molecules while providing space for cell proliferation and migration. Thus in this study, a solvent transfer-induced phase separation (STRIPS)-based technique was developed to make bijels-derived hybrid membrane with good biocompatibility. Bijels membranes having hexanediol diacrylate (HDA) and water phases were produced. HDA was then solidified by UV curing. The channel size in membranes after water removal was 20-100um. Membranes were then immersed in Na-alginate solution, taken out and immersed in CaCl2 solution for crosslinking alginate, resulting in bijels-derived hybrid membranes for tissue engineering. In initial biological studies, human dermal fibroblasts and MC 3T3 cells were cultured on bijels-derived porous HDA for up to 28 days. Results by Live/Dead assay and MTT assay revealed high cell viability and good cell proliferation. SEM and confocal microscopy showed both cells migrated and proliferated well in channels of membranes having average channel sizes larger than 50um. In membranes with smaller channel sizes, both cells exhibited only partial migration into channels.

Authors : Raj Kumar, Orit Shefi, Yogendra Kumar Mishra
Affiliations : Bar-Ilan Institute for Nanotechnology and Advanced Materials (BINA) and Faculty of Engineering, Bar-Ilan University, Ramat Gan 5290002, Israel Functional Nanomaterials Center, Institute of Materials Science, Kiel University, Kaiserstr, 2, D-24143 Kiel, Germany

Resume : There is a growing need for biocompatible nanocomposites that will effectively interact with biological tissues through multiple modalities. However, many new synthesised nanomaterials are limited their use in neural tissue engineering application due to higher cytotoxicity. Hence, synthesis of new materials with good biocompatibility and biodegradability is always in demand for tissue engineering applications. we studied various materials such as gold nanoparticles, silver nanoparticles coated substrates to promote neural differentiation and outgrowth. however, it is two dimensional. Various researchers developing the three-dimensional tissue engineering scaffold such as a hydrogel. However, hydrogel has its own disadvantages and limited to the number of hydrogels only available. Hence, three-dimensional nanomaterials are an emerging source for neural tissue engineering application. Here, we synthesise the ZnO tetrapods microstructures with controlling physicochemical properties. The interaction of zinc oxide tetrapods is investigated with neuronal cells. We studied the cell viability and differentiation of PC12 cells and SH-SY5Y cells. Results showed good biocompatibility and excellent interaction with cells. Controlling organization of Zinc oxide tetrapods structures can be a promising material for 3D neural network outgrowth and scaffold for neural tissue engineering. as a Nanotechnology advanced Carbon dots (CDs) could serve as biocompatible fluorescence nanomaterials for targeted tissues/cell imaging. To achieve this goal, the fluorescence as well as the targeting properties of the CDs should be improved. Herein, we synthesized CDs doped with different metals (Au, Ag, Ga, Zn and Sn) and elements (B, N and P) using acoustic cavitation and hydrothermal methods, respectively. The effects of different experimental parameters on the physico-chemical properties such as size and shape were studied. The prepared CDs showed good quantum yield, minimum cytotoxicity and good cellular uptake when interacted with neural cells. Moreover, doping CDs with metals/elements improved neurites' initiation and elongation when compared with pristine carbon dots. Our research demonstrates the use of CDs for imaging and neuronal interactions. The prepared CDs show promise due to their biocompatibility, photo-stability and potential selective affinity, paving the way for multifunctional biomedical applications.

Authors : Sung Eun Seo, Oh Seok Kwon
Affiliations : Korea Research Institute of Bioscience and Biotechnology (KRIBB)

Resume : Dual-converted fluorescent probe is very useful for monitoring hazard materials for the human being. Especially, heavy metal monitoring methods have been developed for several decades, because of the fatal toxicity and the harmness of the heavy metals such as mercury, lead or cadmium to the human health. Through the development of nanomaterials and surface functionalization method, the field of photoluminescence (PL) point-of-care testing was enabled. Especially, the dual imaging for the detection under only one light source was challenge. In this work, we demonstrated the dual-monitoring system using up/down converted PL nanohybrids under a single light source. Using the PL nanohybrids as the probe, the detection of heavy metal was possible. The fluorescent chemical conjugated nanocapsule showed selective and sensitive performance to mercury ion. Moreover, the dispersion of the fluorescent probe was tracked by upconverted light from the core of the nanocapsule. Their application in the real world can be expanded not only drinking water or tap water, but also the ground surface or the living organisms.

Authors : N.E. Stankova1, N.N. Nedyalkov1, A.S. Nikolov1, P.A. Atanasov1, E. Radeva2, E. Iordanova2, G. Yankov2, V. Mihajlov2, K.N. Kolev3
Affiliations : 1Institute of Electronics, Bulgarian Academy of Sciences, 72 Tzarigradsko Chaussee blvd., 1784 Sofia, Bulgaria, 2Institute of Solid State Physics, Bulgarian Academy of Sciences, 72 Tsarigradsko shousse blvd., 1784 Sofia, Bulgaria, 3Institute of Physical Chemistry, Bulgarian Academy of Sciences, Acad. Georgi Bonchev str. bld.11, 1113 Sofia, Bulgaria

Resume : We present results on three dimensional (3D) photonic effects in optically transparent and flexible media like PDMS polymer by using direct laser processing approaches. Short and ultrashort laser pulses generated in the UV-ViS-NIR spectrum are used for producing of optical waveguide arrays or periodically patterned structures. By controlling the laser parameters like wavelength, fluence, pulse duration, number of pulses, direct laser patterning or ablation can be performed in local surface or volume area without limit of the planar structures. The elasticity of PDMS allows tunable control of the structures’ parameters and hence of the photonic effects induced. This method enables non-clean room and easy controllable fabrication approach of photonic elements spanning from skin or implantable wearables for healthcare monitoring to implantable neural interface devices as well as the chip-scaled optical interconnects. Different techniques (UV-Vis spectroscopy, x-ray photoelectron spectroscopy, optical and scanning electron microscopy) are used for study of optical, compositional and structural properties of the pristine and the laser treated areas.

Authors : N. Tsierkezos, U.Ritter, P.Scharff (1), O.Ivanyuta, E.Buzaneva (2)
Affiliations : 1- TU Ilmenau, Institute for Chemistry and Biotechnology,Postfach 100565, 986 884, Ilmenau, Germany ; 2- TSN University of Kyiv, 64/13 Vladymirska Str.,01033, Kyiv, Ukraine e-mail:

Resume : The advanced study of nanocarbon surface bioactivity allows fundamental investigation and develop biotechnologies for a creation bioactive-compatible materials with smart interfaces due to immobilized surface by nanocarbon coating layer for the bio-activation, protection from virus biomaterials. The direct confirmation of nanocarbon bio-activity is pioneering results at UC of Riverside which demonstrated the topography single bone forming cell on multi-walled carbon nanotubes (MWCNTs) at the interface with hydroxyapatite (Laura Zanello at al., NanoLett., 2006, 6, 562). Also, well known a fundamental investigations carbon surface chemistry and carbon-modified surfaces (carbohydrate coatings) for bio/hemocompatibility of such surfaces (Paula E. Colavita, Trinity College Dublin, Dublin, Ireland). The investigation is aimed to develop a surface bioengineering of nanocarbons by the immobilization of the molecules (fullerenes, carbon nanotubes) in water suspensions for coating formation on biomaterials and to invaluable a bio-behaviour of these new nanomaterials at an interface with biomedical materials ? silicon, titanium, hydroxyapatite. The experimental results for the short MWCNT with high reactivity due to high concentration of end carbon atoms with free bonds and with additionally increased reactivity due to of defect sites on sidewalls in addition to end carbon atoms with free bonds are presented. As a result of the complex optical spectroscopy (UV-visible-NIR, IR- and Photoluminescence Spectroscopes) and imaging investigation (SEM, AFM) of these nanotubes in water suspensions and nanostructures on silicon surface prepared in accordance with developed schemes, we confirm that tubes with sidewall structural defects and immobilizing groups to recognize biomolecules. Then surface biosensing of these nanotubes in a water suspension and on silicon surface, as photoluminescent ones at 450-700 nm, is tested for DNA sequences, biotin, glucose. Also for recognition of these biomolecules was using electrochemical characterization of the short MWCNT layer on silicon surface.

Authors : Seung Min Lee, Kwang-Ho Lee
Affiliations : Advanced Materials Science and Engineering, Kangwon National University

Resume : Flexible and wearable bio-electrode provides a variety of is made from various biocompatible biomaterials that provide safely to achieve a wide range of complexity and functionality. Here, we developed flexible and wearable bio-electrode that could acquire the bio-signals from the skin surface. Multi-layered electrode were encapsulated and used as substrate and its biocompatibility, conductivity, elasticity and acquisition of the electrocardiogram were characterized according to the size of recording site area. The fabricated electrode composes of polyimide and metal layer was fully encapsulated in polydimethylsiloxane which provide flexibility and biocompatibility. To characterize the performance of electrode, three different-sized electrodes were fabricated, and the signal was tested to be enhanced in proportion to the size of the recording site. To ensure electrical safety of fabricated electrode, the leakage current was examined. The developed electrode showed extremely small leakage current compare to direct contact electrode over the range of applied current from 0 to 10 mA. More than 99% of the applied current was prevented from leakage into the surrounding tissues with no inflammation or infection, in contrast to the current leaked from direct-contact electrodes. A flexible and wearable electrode enhanced level of conformal contact with electrical performance by biomimcked environments, bio-signal qualities were successfully achieved. This suggested flexible and wearable electrode may be utilized to monitor several physiological signals without any risks due to the direct metal contact to tissues.

Authors : Lassaad Barhoumi (a, b), Abdoullatif Baraket (c), Mounir Ben Ali (a,b), Abdelhamid Errachid (c)
Affiliations : (a) Higher Institute of Applied Sciences and Technology of Sousse, University of Sousse, Sousse, Tunisia; (b) Nanomisene Lab, LR16CRMN01, Center for Research on Microelectronics and Nanotechnology of Sousse, Sousse, Tunisia; (c) Université de Lyon, Institut des Sciences Analytiques,UMR 5280, CNRS,Université Lyon 1, ENS Lyon-5, rue de la Doua, F-69100 Villeurbanne, France.

Resume : We report in this work, the synthesis and characterization of a novel immunosensor based a screen-printed gold electrode (SPAuE) modified with a new structure of iron magnetic nanoparticles coated with poly (pyrrole-co-pyrrole-2-carboxylic acid, Py-Py-COOH) (Py/Py-COOH/MNP) particles to increase the immunosensor sensitivity of Tumor Necrosis Factor-? (TNF-?). TNF-? antibodies were covalently bonded to Py/Py-COOH/MNP modified SPEAu. A sandwich-type detection strategy was then employed for antigen (Ag-TNF-?) detection through the labeled conjugate antibody (Ab-TNF-?-HRP) activity in a TMB solution. Finally, the chronoamperometry technique was applied to characterize the modified SPEAu. The use of a conjugate antibody anti-TNF-? labeled with horseradish peroxidase (Ab-TNF-?-HRP) was investigated using tetramethylbenzidine (TMB) substrate as electrochemical substrate. The modified screen-printed gold electrode (SPEAu) was characterized for the first time, using atomic force microscopic (AFM) and scanning electron microscopy (SEM). The specificity of the immune-sensor was then investigated under the optimal experimental conditions by analyzing aqueous solutions containing possible interferences represented by other salivary cytokines secreted in the acute stage of inflammation, such as interleukin-6 (IL-6) and interleukin-10 (IL-10). The developed immune-sensor showed good performances for Ag-TNF-? detection within the range of 1 pg mL-1 to 15 pg mL- 1 of antigen TNF-? was determined at 1 pg mL-1. The present immune-sensor is this very promising for sensitive and rapid detection of antigen Ag-TNF-? in clinical sample.

Authors : Qingzhen Bian, Yuxin Xia, Chiara Musumeci, Olle Inganas
Affiliations : Qingzhen Bian, Olle Inganas Department of Physics, Chemistry and Biology (IFM), Linköping University, 58183 Linköping, Sweden.

Resume : To make high-performance bioelectronic devices, a good ohmic contact between the electrode and active layer is required. Ohmic injection based on semiconductor material have been studied, while for the biointerface, since tunnelling phenomena exist, there still need further work to confirm Ohmic injection contribution. Here, we present a new solution processed DNA based hybrid material, and this material demonstrate selectively hole transport property. This new biointerface works well based on diode and transistor structure, demonstrate effectively ohmic injection. Furthermore, we give a detailed information based on experimental results, confirm that Ohmic injection contributes to the device performance. Besides this, the new biointerface demonstrate less surface recombination at collecting contacts. To specify the DNA role, we also done the temperature dependent test (down to 80K). Finally, this biointerface can be used in roll-to-roll technique, enhancing correlated device performance from the large printed flexible device. All these results indicating that this new biointerface works well due to the effective ohmic injection.

Authors : Federica Arena, Giorgio Giuffredi, Andrea Perego, Stefano Donini, Emilio Parisini, Fabio Di Fonzo
Affiliations : Dipartimento di Energia-Politecnico di Milano; Dipartimento di Energia-Politecnico di Milano; CNST-IIT; CNST-IIT; CNST-IIT;CNST-IIT

Resume : Bioelectrochemical system (BES) is an emerging innovation field that synergistically integrates advanced nanotechnology with biotechnology, exploiting the high selectivity and specificity of enzyme immobilized on the surface. In this study, we propose a novel hybrid catalyst for the electrochemical reduction of CO_2 to formic acid. The FDH from Thiobacillus sp. KNK65MA is immobilized on the cathode using a trees-like nanostructurated mesoporous support of Titanium Nitride (TiN) fabricated by Pulsed Laser Deposition (PLD). Thanks to this technique, we realize a support with high surface area improving the bio-interface. By an enzymatic assay, we demonstrate that nanostructuration increases the surface area of the support and favours enzyme immobilization. The efficiency of the system is investigated at different applied potential, showing that during a 3 h reaction period the electrosynthesis of formic acid is 5.3 ±0.4 ?mol with a Faraday Efficiency of 61% under low potential applied of -0,45 V_RHE. Finally, the physical characterization of the hybrid electrode show that the nanostructure does not undergo any important modifications in its morphology and composition after the test, demonstrating the mechanical stability of the TiN scaffold. To conclude, here we demonstrate that the TsFDH|TiN electrode has a great potential in terms of product specificity, stability and sustainability to develop a technology for CO_2 reduction.

Authors : Chiung Wen Kuo and Peilin Chen
Affiliations : Research Center for Applied Sciences, Academia Sincia, Taiwan

Resume : The detection of circulating tumor cells (CTCs) is very important for cancer diagnosis. CTCs can travel from primary tumors through the circulation to form secondary tumor colonies via bloodstream extravasation. The number of CTCs has been used as an indicator of cancer progress. However, the population of CTCs is very heterogeneous. It is very challenging to identify CTC subpopulations with high metastatic potential, such as cancer stem cells (CSCs), which are very important for cancer diagnostic management. We report a study of real-time CTC and CSC imaging in the bloodstreams of living animals using multi-photon microscopy and antibody conjugated quantum dots. We have developed a cancer model for noninvasive imaging wherein pancreatic cancer cells expressing fluorescent proteins were subcutaneously injected into the earlobes of mice to form solid tumors. When the cancer cells broke from the solid tumor, CTCs with fluorescent proteins in the bloodstream at different stages of development could be monitored noninvasively in real time. The number of CTCs observed in the blood vessels could be correlated to the tumor size in the first month and reached a maximum value of approximately 100 CTCs/min after five weeks of tumor inoculation. To observe CTC subpopulations, conjugated quantum dots were used. It was found that CD24+ CTCs can move along the walls of blood vessels and migrate to peripheral tissues. The accumulation of CD24+ cells on the sides of solid tumors was observed, which may provide valuable insight for designing new drugs to target cancer subpopulations with high metastatic potential. We also demonstrated that our system is capable of imaging a minor population of cancer stem cells, CD133+ CTCs, which are found in 0.7% of pancreatic cancer cells and 1-3% of solid tumors in patients. With the help of quantum dots, circulating tumor cells with higher metastatic potential, such as CD 24+ and CD 133+ CTCs, have been identified in living animals. Using our approach it is possible to investigate detailed metastatic mechanism, such as extravasation of tumor cells to the blood vessels. In addition, the number of observed CTCs in the blood stream could be correlated with the stage of tumor.

Authors : Marleine Tamer (a,b), Maria Bassil (b), Sebastien Balme (a), Philippe Miele (a), Mario El Tahchi (b), Mikhael Bechelany (a)
Affiliations : a. Institut Européen des Membranes, ENSCM, CNRS, Université de Montpellier, France. b. Laboratoire des Biomatériaux et Matériaux Intelligents, Département de Physique, Université Libanaise - Faculté des Sciences II, Jdeidet, Liban.

Resume : The kidney plays an essential role in the normal body function. Dialysis is a treatment method used to for blood purification in case of kidney failure or reduction of the efficiency of blood filtration, which causes a socio-economic burden on the patient and society in general [1, 2]. In this work we aim developing a new microfluidic device composed of several ?filtration units? that miniaturize the dialysis system. Each ?filtration unit? encapsulates a smart, adaptive Polyacrylamide (PAAM) hydrogel matrix having specific properties. The polyelectrolyte matrix is the functional unit of the device and acts as an exchange membrane. Using hydrogels having different properties will lead the generation of different filtration units each having a specific function and imitating a specific renal activity. In this work, several 2D hydrogel matrices are prepared and their physicochemical properties are tailored as desired in order to monitor the filtration ability and efficiency of the ?filtration unit?. Controlling the pore size of the matrix will allow monitoring the size selectivity or the molecular weight cutoff while controlling the pores number will help controlling the speed of solute diffusion across the matrix. In addition 3D matrices are developed in order to host cells in some units and will work as bioreactors. The future bioartificial kidney would be an assembly of several filtration units working in parallel. 1. Ota, T., et al. IEEE Micro Electro Mechanical Systems (MEMS). 2018. 2. Ising, C. and P.T. Brinkkoetter, Springer International Publishing: Cham. p. 563-575. 2017.

Authors : L.A. Osminkina 1,2, S.N. Agafilushkina 1, M.B. Gongalsky 1, U.A. Natashina 1, N.Yu. Saushkin 1, E.A. Kropotkina 3, A. A. Kudryavtsev 4, J.V. Samsonova 5, A.S. Gambaryan 3
Affiliations : 1Lomonosov Moscow State University, Physics Department, Leninskie Gory 1, 119991 Moscow, Russian Federation 2Institute for Biological Instrumentation of Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russian Federation 3Chumakov Federal Scientific Center for Research and Development of Immune-and-Biological Products, Russian Academy of Sciences, Moscow, 108819 Russian Federation 4Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Pushchino 142290, Russian Federation 5Lomonosov Moscow State University, Department of Chemistry, Leninskie Gory 1, 119991 Moscow, Russian Federation

Resume : We report results of investigation of binding of porous silicon nanomaterials, i.e. porous silicon films (PSi) and nanoparticles (PSi NPs) with different types of enveloped viruses such as H1N1 influenza A (Flu), Poliovirus (PV1), Human immunodeficiency virus (HIV), West Nile virus (WNV) and Hepatitis virus (HAV). The interaction of the nanostructures and the virions was confirmed by electronic and optical methods. According to TEM images and dynamic light scattering measurements, the virions were stuck to the porous surface of the nanoparticles, which led to the formation of large agglomerates. Such agglomerates were easily precipitated by centrifugation, and that approach was used to clean the suspensions from the viral contamination. Moreover, the discovered binding was useful for optical sensing of the virions absorbed on the PSi surface. This work was supported by Russian Science Foundation (RSF) grant No. 17-12-01386.

Authors : A. Szuplewska, A. Rozmyslowska-Wojciechowska, Sz. Pozniak, M. Chudy, M. Birowska, M. Popielski, B. Scheibe, V. Natu, M. W. Barsoum, J. A. Majewski, A. M. Jastrzebska
Affiliations : Warsaw University of Technology, Faculty of Chemistry; Warsaw University of Technology, Faculty of Materials Science and Engineering; Warsaw University of Technology, Faculty of Materials Science and Engineering; Warsaw University of Technology, Faculty of Chemistry; Faculty of Physics, University of Warsaw; Faculty of Physics, University of Warsaw; NanoBioMedical Centre, Adam Mickiewicz University; Department of Materials Science and Engineering and A. J. Drexel Nanomaterials Institute, Drexel University, Philadelphia; Department of Materials Science and Engineering and A. J. Drexel Nanomaterials Institute, Drexel University, Philadelphia; Warsaw University of Technology, Faculty of Materials Science and Engineering

Resume : The titanium carbides, such as Ti3C2, belong to a new family of two-dimensional nano-materials called MXenes and exhibit in addition to many interesting properties also strong biological activity. However, in spite of intensive research of these materials, the physico-chemical mechanisms determining the biological behavior of titanium carbides are rather poorly understood. Partly, it lies in complex technology employed to synthesize these materials and in the formation on titanium oxides on their surfaces. In this communication, we report joined experimental and theoretical studies of these exciting materials that should shed light on the mechanisms leading to the toxicity of Ti3C3 flakes towards cancerous cells. We fabricated the samples, characterized them carefully, and finally performed ab initio calculations to explain the possibility of formation of the Ti-O bonds and further TiO2 layers on the Ti3C2 surface. Our studies reveal that the formation of TiO2 layer influences the biological activity of the samples regardless of the post-growth treatment employed. We conclude that the presence of TiO2 oxidation layer on the surface of 2D Ti3C2 monolayers should not be considered as a disadvantage when specific bio-action of MXene monolayers is required, however, the interference between oxidation and post-treatment effects on cytotoxicity requires very carefully monitored. Acknowledgements: Support of NCN through the grant SONATA (UMO 2017/26/E/ST8/01073) is acknowledged.

Authors : Seon Joo Park, Oh Seok Kwon*
Affiliations : Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)

Resume : Over the last few decades, significant efforts have been involved to develop rapid, accurate, reproducible and portable diagnostic technologies in science and engineering. Recently, the field-effect transistor (FET) has been used in the development of diagnostic tools. It is gated by changes of charge carrier density in the channel induced by the binding of target molecules, leading to electrical signal. The FET platform is attractive as sensor plaform due to their low cost, easy operation, rapid response, parallel sensing as well as high sensitivity. G-protein-coupled receptors (GPCR) are seven-transmembrane domain receptors, mediate a variety of cellular response. An unique binding event between ligands and receptors causes a conformational change and activate internal transduction, thus resulting in the production of hundreds of second messenger molecules. It has been used as the target for the development of drugs in many clinical indicators. Therefore, the development of a GPCR-conjugated analytical device is highly desired. Herein, we introduced a high performance FET-typed sensor with G-protein-coupled receptor (GPCR) to detect biocide molecules under 100 ng/ml within 100 s. Micro-patterned graphene was used as electrical channel between electrodes for efficient charge carrier transport and integrated with GPCR in the FET system. It exhibited high sensitivity and provided multiple responses toward mixed targets. Moreover, it showed unprecedented reliability and reproducibility in control experiments. It could provide the opportunity a variety of sensor such as disease diagnosis, drug discovery, and food-spoilage in the future.

Authors : Phuong Hoang, Niveen M. Khashab
Affiliations : Smart Hybrid Materials Lab (SHMs), Advanced Membranes and Porous Materials Center (AMPMC), King Abdullah University of Science and Technology (KAUST)

Resume : Identification of a single point mutation in peptide could aid understanding the effect of biostructural changes on protein behavior such as formation of insoluble amyloids. Established techniques to detect the mutation in peptide is either destructive or requires rigorous molecular labeling. We propose a non-invasive and label-free detection method of amino acid (AA) substitution in primary peptide fragments, relying on the analogy between vibrational Raman scattering signal of the amino acids and the peptide. The identification process converts surface-enhanced Raman scattering (SERS) signal of 20 proteinogenic amino acid into a spectral library of representative barcodes and quantifies the correlation between their encoded spectral features with that of peptide fragment. We discover that the specificity of the barcode system was improved when extending the screening region to include high frequency vibrations (2500-3500 cm-1). Coupling with the sensitivity of the designed shell-isolated SERS sensor, the barcoded system can identify amino acids in 15-20 amyloid β peptide and detect single point mutation of Lys28 in the Aβ (25–35) peptide with a detection limit of 10(-5) M.

Authors : Ming-Pei Lu
Affiliations : Taiwan Semiconductor Research Institute, National Applied Research Laboratories, Taiwan

Resume : To meet the needs of the bio-electronic interfacing for the neuronal network and physiological signal transmission applications, highly sensitive and miniaturized electronic elements for the detection of sodium/potassium ions have been of interest. A nanoscale BioFETs composed of the nanowire (NW) have received great attention in the past decades due to their promising applications of biological/chemical sensors、ion-sensitive sensors and nano-bioelectronics. In this NW bioFET system, ions in aqueous solutions can play an important role in determining the surface potential at the liquid-NW interface, accordingly affecting the fundamental electrical characteristics of NW bioFET systems. In this report, we fabricated the p-type NW bioFETs using CMOS-compatible manufacture techniques for exploring the possibility of using NW bioFET as potassium ion-sensitive electronic device for bio-electronic interfacing applications. The sizes of the NW of 77 and 210 nanometers in our silicon NW bioFETs were defined by using the electron-beam lithography technique. Both the back-gate and liquid-gate control modes were adopted for studying the effect of the gate capacitive coupling on the ion-sensitive behaviors in the NW bioFETs. We found that when the NW bioFETs were operated with the back-gate mode, the value of the threshold voltage shift, corresponding to the potassium concentration change, for the 210-nm NW BioFETs was greater than the voltage shift for the 77-nm NW BioFETs. While, under the operation of liquid-gate mode, the 210-nm NW bioFETs showed a smaller voltage shift than that of the 77-nm case. This report provides information about the importance of the gate control mode on the ion-sensitive characteristics of NW bioFETs for bio-electronic interfacing applications.

Authors : Wiktoria Lipińska, Katarzyna Siuzdak, Jacek Ryl, Gerard Śliwiński, Katarzyna Grochowska
Affiliations : The Szewalski Institute IMP PAN, 80-231 Gdańsk, Fiszera 14 st., Poland; Gdańsk University of Technology, 80-233 Gdańsk, Narutowicza 11/12 st., Poland

Resume : The market of non-invasive glucose sensors is drastically growing due to increasing number of people suffering from diabetes. Therefore, there is a significant need for any improvement in the field of biosensors that can be used for monitoring of glucose level in human body. In recent times, the emphasis is put onto the modification of electrode material with enzymes possessing recognition center specific toward particular molecules. In this work, the nanoscale Ti-Au heterostructure functionalized with glucose oxidase (GOx) is reported. Ti-Au material was prepared by anodization of Ti foil, chemical etching, thin Au layer sputtering and finally thermal treatment under continuous regime. The formation of single Au nanoparticles per each structure dimple was revealed by SEM and AFM inspection. In order to confirm enzyme presence and to describe the chemical state of the elements, XPS measurements were performed indicating the complete coverage of Ti-Au material by GOx layer. The obtained electrodes were tested in 0.1 M PBS with an addition of glucose using cyclic and differential pulse voltammetries. The determined linear range, detection limit and sensitivity of tested electrodes satisfy the demands for glucose detection in human body fluids. It was also found that the prepared material is highly reproducible which is of key importance for sensor fabrication. This work was financed by National Center for Research and Development under grant no LIDER/2/0003/L-8/16/NCBR/2017.

Authors : Axel Cordonnier (1,2), Damien Boyer (2), Sophie Besse (1), Arnaud Briat (1), Françoise Degoul (1), Rachid Mahiou (2), Leslie Mazuel (1), Mercedes Quintana (1), Magali Vivier (1), Elisabeth Miot-Noirault (1), Jean-Michel Chezal (1)
Affiliations : (1) Université Clermont Auvergne, INSERM, UMR 1240 IMoST, F-63000 Clermont-Ferrand, France; (2) Université Clermont Auvergne, CNRS, SIGMA Clermont, ICCF, F-63000 Clermont-Ferrand, France

Resume : In recent years, IR-IR upconversion nanoparticles (UCNPs) have shown a great interest in nanomedicine, essentially in medical imaging, due to their ability as imaging agents in the optical window of biological tissues. In this context, NaYF4-based core-shell UCNPs co-doped with Yb3+ and Tm3+ ions were designed to result in 800 nm emission upon excitation at 980 nm. The thermolysis synthesis of those UCNPs was performed one-pot in a mixture of octadecene and oleic acid at high temperature (? 300°C). After purification, samples were characterized structurally (XRD), morphologically (TEM), and their emission spectra were recorded upon 980 nm excitation. DLS measurements were also carried out to determine the UCNPs size, indicating a mean hydrodynamic diameter of 46 nm in accordance with TEM results. The main aim of this work was devoted to the development of multimodal UCNPs for targeting prostate cancer cells by fluorescence imaging and scintigraphy. Thus, radio-labelled hydrophilic UCNPs were prepared by a multi-step process. Firstly, several phosphate-based polyethylene glycol (PEG) ligands were synthesized and exchange method was used to make UCNPs water-soluble. PEGs used for ligand exchange include azide group to conjugate both PSMA targeting ligand and radiolabelled prosthetic group to the UCNPs by bio-orthogonal chemistry. Competition binding assays in LnCAP cell lines showed a good affinity of PSMA ligands toward their target. Finally, synthesis of fully functionalized UCNPs are ongoing. They will be tested in vitro and in vivo against PSMA-expressing prostate cancer cells/tumours to assess the efficiency of active targeting and their optical/scintigraphic imaging properties.

Authors : T.H.X. Le,1,2,3,4, M. Xu,1,2,3,4, M. Etienne,1 Lin Zhang,1 N. Vilà,1 F. Lapicque,2 A. Hehn,3 A. Celzard,4 A. Walcarius1
Affiliations : 1 LCPME, UMR 7564 CNRS - Université de Lorraine, 405 rue de Vandoeuvre, 54600 Villers-lès-Nancy, France. 2 LRGP, UMR 7274 CNRS - Université de Lorraine, 1 rue Grandville, 54000 Nancy, France 3 LAE, UMR 1121 INRA–Université de Lorraine, 2 avenue de la Forêt de Haye, 54500 Vandœuvre-lès-Nancy, France 4 Institut Jean Lamour, UMR 7198 CNRS – Université de Lorraine, 27 rue Philippe Séguin, 88000 Epinal, France

Resume : The natural molecules of secondary metabolism produced by plants often have interesting pharmaceutical or cosmetic properties. The structure of these molecules is very complex, making their chemical synthesis almost impossible. To overcome this problem, one solution is to produce the enzymes responsible for their synthesis in plants and to use them in vitro to synthesize the molecules of interest from commercially available precursors. In plants, cytochromes P450 are described as being responsible for the synthesis of a large number of molecules of secondary metabolism. These enzymes are membrane monooxygenases which must be associated with NADPH P450 reductases. This reaction requires the presence of the NADPH cofactor, which is then a limiting and relatively expensive element. The goal of this work is to implement an electrochemical device allowing the use of cytochromes P450 to biosynthesize molecules of interest. For that, we have explored the covalent immobilization of a rhodium complex mediator ([Cp*Rh(bpy)Cl] ) on the surface of porous electrodes for NADPH regeneration. In this communication, we want to highlight the different strategies that we have studied, including diazonium electrografting, click-chemistry and metal complexation [1-3]. [1] L. Zhang et al., ChemElectroChem. 5 (2018) 2208–2217. [2] L. Zhang et al., ChemCatChem. 10 (2018) 4067–4073. [3] L. Zhang et al., ACS Catal. 7 (2017) 4386–4394. This work was supported by the French PIA project « Lorraine Université d’Excellence », reference ANR-15-IDEX-04-LUE.

Authors : F. Decataldo, M. Barbalinardo, M. Tessarolo, M. Calienni, D. Gentili, F. Valle, M. Cavallini,B. Fraboni
Affiliations : F. Decataldo; M. Tessarolo; M. Calienni; B. Fraboni - Department of Physics and Astronomy, University of Bologna, Italy M. Barbalinardo; D. Gentili; F. Valle; M. Cavallini - Instituto per lo Studio dei Materiali Nanostrutturati (ISMN), Centro Nazionale delle Ricerche (CNR), Bologna, Italy

Resume : Semiconducting polymers are very promising materials for biomedical application, thanks to their ability to conduct both ions and electrons, their biocompatibility and their flexible and soft mechanical properties. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) has high conductivity, electrochemical and thermal stability in aqueous environment and reversable electrochemical properties that render it suitable as smart nano-biointerface with biological elements and environment. In our work, we present PEDOT:PSS-based Organic Electrochemical Transistors (OECTs) for the electrical continuous monitoring of CaCo-2 and NIH-3T3 viability and their reaction to exogenous toxic agents, providing an easy, fast and real-time way overcoming standard optical evaluation techniques. Cells are directly grown on thin PEDOT:PSS thin film OECTs: the presence of a cell monolayer slows down ions flowing from the electrolyte in the semiconducting polymer, thus giving an electronic readout of cell layer integrity and health. Noteworthy, a suitable pattern of the dimensions of devices allows the study of different kind of cells, even leaky-barrier or non-barrier cell lines commonly not suitable for electrical monitoring. We demonstrated that our PEDOT:PSS OECTs provide a simple, low-cost and dynamic biosensors able to monitor leaky-barrier cell culture growth and stress response induced by drug treatments, paving the way for high throughput and low-cost screening of drug discovery or toxicology.

Authors : U.A. Natashina, M.B. Gongalsky, A. A. Kudryavtsev, L.A. Osminkina
Affiliations : Department of Physics, Lomonosov Moscow State University, Leninskie Gory 1, 119991 Moscow, Russian Federation; Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Pushchino 142290, Russian Federation; Institute for Biological Instrumentation of Russian Academy of Sciences, 142290 Pushchino, Moscow Region, Russia

Resume : The advantages of porous silicon nanoparticles (PSi NPs) are associated with their low cytotoxicity and good biodegradability in physiological fluids and in living tissues. In this study such informative optical methods as Raman micro-spectroscopy and photoluminescence spectroscopy as well as confocal microscopy were employed for diagnostics of biodegradation of PSi NPs in simulated suspensions and living cells. We used 100 nm nanoparticles with pore diameters of 15±5 nm and specific surface area of 230 m2/g. PSi NPs have been found to have stable structural and optical properties for at least 6 months when stored in water at high concentrations. However, when incubated with cells or when introduced into model biological solutions, the nanoparticles began to dissolve. The PSi NP dissolution processes were studied by changes in their Raman spectra, where a low-frequency shift of the signal maximum, its broadening and a decrease in intensity are observed. Also during the process of dissolving of PSi NPs, their photoluminescence first flared up and then dramatically dropped, which was also noticeable when visualizing nanoparticles in living cells. The reason for this is the decrease in the size of silicon nanocrystals, in which phonon and quantum confinement effects occur. This work was supported by Russian Science Foundation (RSF) grant No. 17-12-01386. UAN also acknowledges the scholarship of the Foundation for Development of Theoretical Physics and Mathematics "BASIS".

Authors : M. B. Gongalsky, A. A. Koval, S.N. Agafilushkina, and L. A. Osminkina
Affiliations : Lomonosov Moscow State University, Physics Department, Leninskie Gory 1, 119991 Moscow, Russian Federation

Resume : We report on highly sensitive optical detection of bacteria via efficient adhesion on the surface of new nanostructurized material called double etched porous silicon (DEPSi). DEPSi was obtained by two-stage etching process, i.e. 1) electrochemical etching of monocrystalline Si wafers in hydrofluoric acid solutions, which resulted in formation of mesoporous silicon layer (pore diameter was about 5-15 nm), and 2) metal-assisted chemical etching (MACE) of the porous layers, which created bigger pores or holes with diameter in the range of 100-1000 nm. DEPSi was demonstrated to be a good compromise between perfectly flat structures required for efficient optical detection and rough surfaces with high affinity to bacteria. The surface of the DEPSi had a lot of cavities and holes, which acted like traps for bacteria. Detection of bacteria (E. Coli) was performed by two optical methods, i.e. infrared spectroscopy and interferometry. The first approach revealed chemical bonds (C=C) typical for the bacteria on the surface of DEPSi. The second one used the DEPSi layer as a Fabry-Perot interferometer. In the presence of the bacteria, interferograms were changed, and Fast Fourier transform analysis of the reflectance spectra showed reversible broadening and shift. This allowed detection of the bacteria with sensitivity higher than 10 000 colony-forming units per mL. This work was supported by the Russian Science Foundation (RSF) grant No. 17-12-01386.

Authors : Marta d?Amora1 and Silvia Giordani1, 2
Affiliations : 1 Nano Carbon Materials, Istituto Italiano di Tecnologia, Via Livorno 60, 10144, Turin, Italy 2 School of Chemical Sciences, Dublin City University, Dublin, Ireland

Resume : Carbon nano-onions (CNOs) are a class of promising carbon nanomaterials for biomedical applications. Functionalized CNOs show high cellular uptake and low cytotoxicity and fluorescently labeled CNOs (f-CNOs) are excellent platforms for biological imaging. Although CNOs present promising toxicity profiles, evaluations in complex models are required to corroborate biosafety concerns. Zebrafish (Danio Rerio) present numerous peculiarities in comparison to other vertebrates, enabling fast assessments of nanomaterial toxicity [1]. CNOs are more biocompatible in comparison to other carbon nanomaterials, including carbon nano-horns, nano diamonds and graphene oxide [2]. In this study, the biological interactions of f-CNOs in zebrafish during the development are investigated in terms of biosafety assessment and biodistribution [3]. Different toxicological endpoints are evaluated in embryos/larvae treated with f-CNO, including swimming and cardiac activities. Moreover, the biodistribution of f-CNOs is determined at different stages of growth, using advanced fluorescent microscopy techniques. Our results reported the biosafety of f-CNOs and their specific biodistribution in zebrafish. References [1] M. d?Amora, S. Giordani, Frontiers in Neuroscience, 2018, 12, 976. [2] M. d?Amora, A. Camisasca, S. Lettieri, S. Giordani, Nanomaterials, 2017, 7(12), 414. [3] M. d'Amora, M. Rodio, G. Sancataldo, R. Brescia, F. Cella Zanacchi, A. Diaspro, S Giordani, Scientific Reports, 2016, 6, 33923.

Authors : M.B. Gongalsky1,2, A.P. Sviridov1, V.D. Egoshina1, G.Z. Gvindzhilia1, A.A. Kudryavtsev3, V.G. Andreev1, M.J. Sailor2, L.A. Osminkina1
Affiliations : 1 Lomonosov Moscow State University, Faculty of Physics, Russia 2 University of California San Diego, Department of Chemistry and Biochemistry, USA 3 Institute of Theoretical and Experimental Biophysics, Russian Academy of Science, Russia

Resume : We prepared porous silicon nanoparticles (PSiNPs) with amphiphilic properties, i.e. outer surface of PSiNPs was hydrophilic in order to provide good biocompatibility of the particles, while inner surface was hydrophobic. Initial mesoporous silicon layers were coated by hydrophobic octadecylsilane (ODS), then they were fractured to 200-nm PSiNPs in a mixture of ethanol and water in a planetary ball mill. This procedure also created a hydrophilic surface. Hydrophobic surface inside PSiNPs amplifies cavitation under ultrasonic activation, which resulted in a twofold decrease of cavitation threshold at frequency of 2.08 MHz. Experiments in vitro revealed 20% decrease of ultrasonic intensity threshold for cells viability in the presence of 0.5 mg/ml of PSiNPs. This can be used for the selective ultrasonic treatment of cancer tumors after targeting of PSiNPs. Near-infrared photoluminescence of PSiNPs (quantum yield was about 5%) was activated by sodium tetraborate treatment before ODS functionalization. Efficient luminescence provided visualization of PSiNPs in living cells. Thus PSiNPs are promising agents for theranostic applications. This work was supported by the Russian Science Foundation Grant N 17-72-10200.

Authors : Ruma Maity, P. S. Burada
Affiliations : Dept. of Physics, Indian Institute of Technology Kharagpur ; Dept. of Physics, Indian Institute of Technology Kharagpur.

Resume : The swimmer here is chiral in nature. A chiral squirmer can rotate while translate in the fluid medium. This is an advantage for the body as it can adjust its direction of motion by adjusting its rotational motion while sensing an external chemical stimulus. Here we have considered an unsteady chiral squirmer which performs a periodic motion in the fluid medium. This has been modelled with a time-dependent active slip velocity on the surface. In the presence of a chemical stimulus the system responds to it by an adaptation and relaxation mechanism. The body eventually alters its time-dependent restricted motion through the modification of the coefficients of the slip velocity after sensing the stimulus. We study how the sensing of the stimulus depends on the strength of the gradient and frequency of oscillation of the body. This study is useful in designing artificial swimmer which is able to chemotax.

Authors : Alessandro Iannaci, Adam T. Myles, James A. Behan, Thomas Flinois, Frédéric Barriere, Eoin Scanlan, Paula E. Colavita
Affiliations : Alessandro Iannaci; Adam T. Myles; James A. Behan; Paula E. Colavita School of Chemistry, CRANN and AMBER research centres, Trinity College Dublin, College Green, Dublin 2; Thomas Flinois; Frédéric Barriere Univ Rennes, CNRS, Institut des Sciences Chimiques de Rennes, France

Resume : Scientific efforts are nowadays focused on the reduction of pollution levels in the atmosphere through harnessing and effective exploitation of renewable and sustainable energy resources. Fuel cells offer a unique combination of benefits that make them a vital technology ideally suited to replace/serve important segments of our energy infrastructures due to their high-efficiency conversion of chemical energy to electricity with low environmental impact. An innovative class of fuel cells, called Microbial fuel cells (MFCs) leverages the ability of bacteria to produce electricity via the digestion of organic matter such as domestic wastewater as fuel. However the performance of MFCs remains modest for practical applications. In this presentation we discuss work towards improving MFC performance via tailored interfacial interactions. Improved adhesion of biofilms to the electrodes is expected to enhance MFC power outputs. Modification of anode materials with biomolecule derivatives of aryldiazonium salts is investigated as a means of modulating biofilm adhesion. Electrografting of in situ generated cations on graphite anodes was found to result in changes on the rate of biofilm development, thus affecting the polarisation/power density output. The role of wetting and biorecognition on biofilm development was investigated via screening of biomolecule derivatives.

Authors : Jinyeong Kim , Oh Seok Kwon
Affiliations : Korea Research Institute of Bioscience and Biotechnology (KRIBB)

Resume : It is necessary to develop interfacing compounds for immobilizing the bioprobes, including an antibody, aptamer, natural receptors and so on, on the platform of biosensors which are consisted of 2D nanostructure. There are various 2D nanomaterials in the literatures. In particular, a graphene has high-conductivity, so the graphene-integrated biosensors have been constructed to enhance their sensitivity and selectivity. However, the surface of the graphene is highly stable owing to their non-covalent electron pairs, so that their surface modification is challenge. In this study, we demonstrated a new technology for graphene interfacing technologies. The new compounds can be easily attached on the graphene surface and provide functional groups at the end of the chemical compounds. Moreover, we proposed a simple protocol for immobilizing the natural receptors on the graphene surface in field-effect transistor system (FET). The receptor-conjugated graphene FET showed high sensitivity and selectivity toward biocides, odorants, and decomposition.

Authors : Hiroya Abe, Hiroshi Yabu
Affiliations : WPI-AIMR, Tohoku University, Japan

Resume : Polydopamine (PDA), which is easily formed by the auto-oxidative polymerization of dopamine. We have previously reported a self-assembled formation of thin polydopamine film (nm-scale) at air/water and oil/water interface. Although the film formed at the air/water interface can be transferred on solid substrates, some cracks appeared during the process, and the film was not stable when the vessel was slightly shaken. To improve a mechanical fragility of PDA films obtained from the air/water interface, we added the polymer containing amino group to the dopamine solution since dopamine and these groups were conjugated via Michel addition and Shiff base reaction. We present self-assembled composite films consisting of polydopamine and gelatin which is known as a biocompatible polymer and has amino group. Dopamine (10 mg/mL) and gelatin (100 mg/mL) were dissolved in Tris-HCl solution (pH 8.9). The brown-colored composite film was self-assembly formed at the air/water interface after 24 hours. The film picked up from the air/water interface was gel-like, robust and flexible. From an SEM cross-sectional image, the thickness of the dried film was over 100 μm. Additionally, by forming 3 dimensional (3D) shaped air/water interface with a sacrifice, 3D structured polydopamine composite films such as a rod and tube shape were obtained. From above results, we successfully obtained robust 2D and 3D polydopamine composite films via self-assembly process.

Authors : Stefania Lettieri, Debora Russo, Ilaria Penna, Adalberto Camisasca, Tiziano Bandiera, Silvia Giordani
Affiliations : Stefania Lettieri, Nano Carbon Materials, Istituto Italiano di Tecnologia (IIT), via Livorno 60, 10144, Turin, Italy; Debora Russo, D3 - PharmaChemistry Facility, Istituto Italiano di Tecnologia (IIT), via Morego 30, 16163, Genoa, Italy; Ilaria Penna, D3 - PharmaChemistry Facility, Istituto Italiano di Tecnologia (IIT), via Morego 30, 16163, Genoa, Italy; Adalberto Camisasca, Nano Carbon Materials, Istituto Italiano di Tecnologia (IIT), via Livorno 60, 10144, Turin, Italy; Tiziano Bandiera, D3 - PharmaChemistry Facility, Istituto Italiano di Tecnologia (IIT), via Morego 30, 16163, Genoa, Italy; Silvia Giordani, Nano Carbon Materials, Istituto Italiano di Tecnologia (IIT), via Livorno 60, 10144, Turin, Italy - School of Chemical Sciences, Dublin City University, Glasnevin, Dublin 9, Ireland

Resume : Carbon nano-onions (CNOs) [1] are multi-shell fullerenes, structured by concentric shells of sp2 carbon atoms. These materials can be easily produced in high quantities by thermal annealing of detonation nano-diamonds. CNOs represent an interesting platform for imaging and diagnostic applications [2] due to their spherical shape, small size, and low toxicity both in vitro [2] and in vivo [3]. In this work we developed a nano-carrier based on 5nm CNOs functionalized with folic acid for potential targeted delivery applications. We decorated the folic acid functionalized CNOs with a chemotherapeutic agent, doxorubicin, using a non-covalent functionalisation strategy and evaluated their specificity and cytotoxicity towards the cancer cell line HeLa CCL2. Robust characterization techniques, such as infrared and absorbance spectroscopy, thermogravimetric analysis (TGA), and X-ray photoelectron spectroscopy (XPS), confirmed the successful functionalization of the nano-carriers with the drug. Our findings indicated the cyto-compatibility of functionalized CNOs without doxorubicin. On the other hand the presence of folic acid on the nano-carrier is key to selectively drive the drug inside the cells, and ultimately causing their death. Our functionalized CNOs, selective for and rapidly up-taken by cancer cells, can open new opportunities for low-cost and biocompatible platforms capable of in vivo selective tumor accumulation of a drug. [1] Bartelmess, J. and Giordani, S. Beilstein J. Nanotechnol. 2014, 5, 1980. [2] Lettieri, S.; Camisasca, A.; d?Amora, M.; Diaspro, A.; Uchida, T.; Nakajima, Y.; Yanagisawa, K.; Maekawa, T.; Giordani, S. RSC Adv. 2017, 7, 45676 [3] d?Amora, M.; Camisasca, A.; Lettieri, S.; Giordani, S. Nanomaterials 2017, 7, 414

Authors : 1) Seong Soo Choi, Sae-Joong Oh, 2) Myoung Jin Park 3) Byung Seong Bae
Affiliations : 1) Research Center for NanoScience, SunMoon University, Ahsan, Chungnam, 31460 South Korea 2) Department of Physics, Korea Military Academy, Seoul, Korea 3) School of electronics and display engineering, Hoseo University, South Korea

Resume : About sixty years ago, the biological cell counter with an electrical currents detection technique through a micrometer size orifice was invented by Dr. Coulter. A couple of years ago, the ultrafast portable pore device (MinION) with an electrical detection technique was manufactured by Oxford Nanopore Technology. However, high error rates over 80 % from this solid state nanopore device is initially reported in several journals. The high error rates may have been contributed from the electrical double layer formed in the pore channel. Even though the error rates have been reduced significantly. Considering the fact that most biosensors are utilizing the optical detection technique and the carbon filters have a slit-type structure with ~ 5 nm gap, the optical slit pore device can be an excellent candidate for the next generation single molecule sensor. We will report the fabrication process of the plasmonic optical slit nanopores

Authors : J.J. Gutiérrez Moreno 1-2, K. Pan 1, W. Li 1.
Affiliations : 1. Institute for Advanced Study, Shenzhen University, Shenzhen 518060, China. 2. Key Laboratory of Optoelectronic Devices and Systems of Ministry of Education and Guangdong Province, College of Optoelectronic Engineering, Shenzhen University, Shenzhen 518060.

Resume : The use of biomaterials such as diatom silica frustules is highly attractive for removing toxic metals from aquatic environments due to their low-cost and abundant supply from natural biomineralization. However, diatoms are composed by an amorphous SiO2 core, which posses very limited properties. Therefore, new approaches are needed to functionalize diatom-based nanostructures to expand their range of useful properties while preserving or appropriately modifying its original nanostructure. In this work, we carry out a systematic density functional theory (DFT) study on the adsorption mechanism of heavy metals and simple biomolecules at several surface-modified crystalline and amorphous silica surfaces. Our results show that the involvement of various functional groups such as surface silanol (SiOHx) or amino groups enhance the diatom capacity to absorb heavy metals like Hg or Cd. The outcomes of these simulations give us a comprehensive insight on the adsorption mechanism of heavy metals at silica-based materials and can be used to support experiments for the development of novel adsorbents biomaterials for their use in environmental applications.

Authors : Sirinrath Sirivisoot
Affiliations : Biological Engineering Program, Faculty of Engineering, King Mongkut's University of Technology Thonburi, Bangkok 10140, Thailand

Resume : The ability to detect bone extracellular matrix proteins would be beneficial for developing a diagnostic tool for measuring bone growth juxtaposed to an orthopaedic implant. Osteocalcin, osteopontin, osteonectin, and bone sialoprotein are important proteins of bone-forming cells that are secreted during osteoblast differentiation and bone extracellular matrix formation. Electrochemical behaviors assessed by cyclic voltammetry of osteocalcin, osteopontin, osteonectin, and bone sialoprotein demonstrated that anodized titanium electrodes with an electrodeposited coating of graphene oxide were able to detect these proteins by graphene oxide-mediated electron transfer. The increased sensitivity produced by coating the anodized titanium electrodes with graphene oxide for detecting low concentrations of proteins might be due to the increased surface area and improved electron transfer of the electrodes. Importantly, the level of secreted osteoblast proteins detected using the modified electrodes indicated the presence of bone formation and matrix mineralization. This study revealed that osteoblast proteins could be detected using anodized titanium electrodes coated with graphene oxide by electrodeposition, and this method could be used for developing a new in-situ sensor to detect bone growth for orthopaedic diagnostics.

Authors : Rou Jun Toh1, Richard Evans1, Helmut Thissen1 and Vincent Ball 2,3
Affiliations : 1: CSIRO Manufacturing, Research Way, Clayton, 3168, Victoria, Australia. 2: Université de Strasbourg. Faculté de Chirurgie Dentaire. 8 rue Sainte Elizabeth. 67000 Strasbourg. France. 3: Institut National de la Santé et de la Recherche Médicale. Unité Mixte de Recherche 1121. 11 rue Humann. 67085 Strasbourg. Cédex. France.

Resume : The synthesis of biocompatible films from aminomalonitrile (AMN) based solutions is a new versatile surface functionalisation method using a precursor molecule which may have played an important role in prebiotic chemistry. We will describe the electrodeposition of AMN based films [1] and we will show in this presentation that the deposition from solution is preceded by a lag phase which duration is dependent on the solution concentration of the precursor. The deposition process was followed by means of quartz crystal microbalance with dissipation monitoring as well as by UV -vis spectroscopy, leading to the estimation of the film deposition rate. For all the investigated solution concentrations, the obtained films are superhydrophilic after long reaction times (>10 h). During deposition, the AMN based deposits undergo morphological and compositional changes. Of the highest interest is the different composition of the films deposited on silicon with respect to the composition of the AMN based aggregates formed in solution; suggesting that the surface allows to control the chemical pathway leading to the final material. This is of particular interest from the point of view of prebiotic Chemistry. [1] Ball, V.; Toh, R.J.; Voelcker, N.,; Thissen, H.; Evans, R. (2018) Electrochemical deposition of aminomalonotrile based films. Colloids and Surfaces A: Physicochem. Eng. Asp. 552, 124-129.

Authors : Sathi Roy, Neus Feliu, Wolfgang J. Parak*
Affiliations : Fachbereich Physik und Chemie, and Center for Hybrid Nanostructure (CHyN), Universität Hamburg, Hamburg, Germany.

Resume : Abstract Intracellular delivery of nanocarriers containing different biopharmaceuticals requires the release of the nanocarriers to the cytosol by endosomal escape.1 Various researches are going on to develop efficient nanocarriers made of different pH-sensitive polymers, which can trigger endosomal escape, by pH-induced structural change. Poly(ethylenimine) (PEI) is one of such pH-sensitive polymer, which has been widely explored for non-viral gene delivery and for designing Nanocarrier vehicle, efficient for therapeutic release to the cytosol. The mechanism behind high efficiency of PEI for endosomal escape has been explained by the well-accepted Proton-sponge hypothesis.2 This hypothesis emphasizes high buffering capacity of PEI inside lysosome along with a subsequent increase in lysosomal pH is the main factor behind the endosomal escape. However, evidence, which proves lysosomal pH change in presence of PEI, remains questionable. Herein we are using SNARF loaded polyelectrolyte capsule as an intracellular pH sensor to study whether PEI can modulate lysosomal pH. SNARF is a pH sensitive dye and it has dual emission property which enables ratiometric pH sensing without using any other reference fluorophore. Loading SNARF inside capsule offers several potential advantages.3 This capsule system has been used to measure pH of lysosome in presence of different branched and linear PEI at different concentration and different exposure time by Flow cytometry analysis. A detailed quantitative study has been performed to understand the proton sponge effect of PEI and its role on endosomal escape. References (1) Forrest, M. L.; Pack, D. W. Molecular Therapy 2002, 6, 57. (2) Creusat, G.; Rinaldi, A. S.; Weiss, E.; Elbaghdadi, R.; Remy, J. S.; Mulherkar, R.; Zuber, G. Bioconjug. Chem. 2010, 21, 994. (3) Kantner, K.; Ashraf, S.; Carregal-Romero, S.; Carrillo-Carrion, C.; Collot, M.; del Pino, P.; Heimbrodt, W.; Jimenez de Aberasturi, D.; Kaiser, U.; Kazakova, L. I.; Lelle, M.; Martinez de Baroja, N.; Montenegro, J.-M.; Nazarenus, M.; Pelaz, B.; Peneva, K.; Rivera Gil, P.; Sabir, N.; Schneider, L. M.; Shabarchina, L. I.; Sukhorukov, G. B.; Vazquez, M.; Yang, F.; Parak, W. J. Small 2015, 11, 896.

Authors : Yongchai Kwon
Affiliations : Graduate school of Energy and Environment, Seoul National University of Science and Technology

Resume : Enzymatic biofuel cells (EBC) using glucose and oxygen fuels are devices converting chemical energy of the fuels to electrical energy by enzyme based biocatalysts. Since the EBC can operate even in physiological conditions, glucose and oxygen contained in human body fluid can be utilized as the fuels for implantable devices. However, in spite of that, there are still problems to be addressed. As one of them, there is a slow reaction rate of the biocatalyst. To solve the problem, introducing a new mediator with the enzyme and substrate materials can be considered. When the mediator is applied, electron transfer for both anodic and cathodic reactions is facilitated and the associated reaction rate, followed by the produced current, is enhanced. To optimize the electron transfer, here, we suggest a new electron transfer mechanism, so called, a mediator embedded electron transfer (EMET). According to our EMET mechanism, mediator properly immobilized onto the enzyme and substrate materials shuttles the electron effectively and as a result, the drawbacks of conventional direct or mediator electron transfer mechanism can be alleviated. In this regard, when it comes to anode, glucose oxidase (GOx) enzyme and dye mediator are used for the purpose and as for cathode, GOx and porphyrin mediator are used. By the use of the redox couple, the activity of the biocatalysts and the performance of EBCs using the biocatalysts were excellent. In this conference, I will explain the related electron transfer theory, the synthetic procedure of corresponding biocatalysts and the configuration and performance of EBC utilized.

19:00 Graduate Student Award ceremony followed by the social event    
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Nanomaterials for biosensing and biodelivery II : Nicolas Brun
Authors : Silvia Giordani
Affiliations : School of Chemical Sciences, Dublin City University, Dublin, Ireland

Resume : Multi-shell fullerenes, known as carbon nano-onions (CNOs), are structured by concentric shells of carbon atoms and are emerging as platforms for biomedical applications because of their ability to be internalized by cells and low toxicity. [1]. In my research group we have developed a synthetic multi-functionalisation strategy for the introduction of different functionalities (receptor targeting unit and imaging unit) onto the surface of the CNOs The modified CNOs display high brightness and photostability in aqueous solutions and are selectively taken up by different cancer cell lines without significant cytotoxicity. [2]. To probe the possible applications of CNOs as a platform for therapeutic and diagnostic interventions on CNS diseases, we injected fluorescent CNOs in vivo in mice hippocampus. We analyzed ex vivo their diffusion within brain tissues and their cellular localization by confocal microscopy, electron microscopy, and correlative light-electron microscopy techniques. The subsequent fluorescent staining of hippocampal cells populations indicates they efficiently internalize the nanoparticles. Furthermore, the inflammatory potential of the CNOs injection was found comparable to sterile vehicle infusion, and it did not result in manifest neurophysiological and behavioral alterations of hippocampal-mediated functions [3]. These results encourage further development as brain disease-targeted diagnostics or therapeutics nanocarriers. [1] S. Giordani et al., Current Medicinal Chemistry 2018, in press. [2] M. Frasconi et al., Chem Eur J 2015, 21 (52), 19071. [3] M. Trusel et al., ACS Appl. Mat. & Inter. 2018, 10 (20), 16952.

Authors : David Beke, Gabriella Dravecz, Gyula Károlyházy, Tibor Z Jánosi, János Erostyák, Katalin Kamarás, Adam Gali
Affiliations : Wigner Research Centre for Physics; Wigner Research Centre for Physics; Wigner Research Centre for Physics; University of Pécs, Szentágothai Research Centre; University of Pécs, Szentágothai Research Centre; Wigner Research Centre for Physics; Wigner Research Centre for Physics;

Resume : Nanoparticles (NPs) have many diverse applications in life- and physical sciences. There is a tremendous interest in understanding the impact of the nanoparticle systems on the living organisms as the interaction determines the physiological response and effects of the NPs on living systems, including cellular uptake, circulation lifetime, signalling, therapeutic effects, and toxicity. Proteins are able to adsorb onto the surface of larger NPs forming a dense protein coating known as protein corona. Considering that most plasma proteins present a hydrodynamic diameter of about 3-15 nm, the behaviour of NPs < 3 nm in biological systems, could be dramatically different from that of larger particles. We propose that restricted diffusion behaviour of the ultrasmall nanoparticles (USNPs) in the vicinity of the proteins should be considered as an additional reaction type when NPs interact with proteins using silicon carbide NPs and BSA as a model system. The transient particle?protein associations can manifest themselves in a physical complex formation that determines the characteristics. The biological behaviour of silicon carbide USNPs in a medium modelling a living organism was investigated in detail. The interaction shows transient nanoparticle-protein associations due to the restricted diffusion behaviour of the nanoparticle in the vicinity of a protein. By studying silicon carbide NPs in different sizes, it can be concluded, that the transient effect is an USNP behaviour.

Authors : You Jung Chung, Byung Il Lee, Chan Beum Park
Affiliations : Korea Advanced Institute of Science and Technology (KAIST)

Resume : Carbon dots (CDs), a new class of zero-dimensional nanomaterials, have attracted great interest in the nanomedicine because of their versatile merits such as biocompatibility, facile functionalization, and tunable photoluminescence. Here, we present the new design of CDs that highly inhibit the aggregation of amyloid-? (A?) peptides. The abnormal aggregation of A? peptides is a major hallmark of Alzheimer?s diseases (AD) that affects 11% of people aged over 65. Despite numerous researches, effective suppression of A? aggregation is still challenging due to multifactorial pathogenesis involving high levels of metal ions in the brain; copper ions (Cu(II)) have drawn significant attention in AD pathogenesis because of their high activities in forming neurotoxic A?-Cu(II) aggregates. To provide a new strategy in the prevention of Cu(II)-associated A? aggregation, we have synthesized the multifunctional CDs that are capable of (1) Cu(II) coordination, (2) interrupting A? self-assembly, and (3) oxidizing A? residues. Nitrogen-containing moieties of as-prepared CDs did a key role in interact with Cu(II) and A??s aggregation sites by electrostatic and hydrogen/hydrophobic interactions. Interestingly, Cu(II)-bound CDs enhanced their fluorescence, further induced the generation of reactive oxygen species (ROS) under light irradiation. The resulting ROS then photodynamically oxidized A? residues (e.g., histidine) to lose the affinity towards Cu(II) and A??s aggregative property. The CDs? simultaneous inhibitory effects significantly mitigated the neurotoxicity of A?-Cu aggregates, showing 96% of cell viability. Our work highlights the therapeutic potential of CDs for future A?-targeted AD treatments.

Authors : Salima El Yakhlifi (1) Marie-Hélène Metz-Boutigue (1,2) Daniel Hauser (3) Barbara Rothen-Rutishauser (3) Ovidiu Ersen (4)
Affiliations : (1) Institut de la Santé et de la Recherche Médicale, Unité Mixte de Recherche 1121, 11 rue human, Cedex, 67085 Strasbourg, France. (2) Faculté de Chirurgie dentaire, Université de Strasbourg, 8 rue Sainte Elisabeth, 67000 Strasbourg, France. (3) Adolphe Merkle Institute, University of Fribourd, 4 chemin des verdiers, CH-1700 Fribourg, Switzerland (4) Institut de Physique et de Chimie des matériaux, UMR 7504 CNRS, Université de Strasbourg, 23 rue du Loess, BP43 Cedex 2, 67034 Strasbourg, France.

Resume : Polydopamine (PDA) formed by the oxidation of dopamine is a substance that can coat the surface of almost all known materials? surfaces. However, its synthesis is usually accompanied by the production of amorphous precipitates in solution. The similarities observed between the PDA and eumelanin, the black brown pigment responsible for the coloration of the skin and hairs, induced to produce stable and size-controlled nanoparticles in solution. Inspired by the presence of proteins in natural eumelanin grains, we could demonstrate that a specific diad of amino acids in proteins [1], namely KE, allows for a specific control in the formation of PDA nanoparticles. We then demonstrated that colloidally stable PDA@protein nanoparticles, which are biocompatible in addition, can be obtained in acidic conditions, where spontaneous auto-oxidation of dopamine is suppressed, using sodium periodate as the oxidant and a protein, like alkaline phosphatase (ALP), as a templating agent [2]. The size of the obtained PDA@ALP nanoparticles depends on the dopamine/enzyme ratio and they display the enzymatic activity of alkaline phosphatase, with an activity extending up to two weeks after particle synthesis. These PDA@ALP nanoparticles can be incorporated in polyelectrolyte multilayered films to potentially design model biosensors or can be used as additives for biocompatible hydrogels. [1] Bergtold, C.; Hauser, D.; Chaumont, A.; El Yakhlifi, S.; Mateescu, M.; Meyer, F.; Metz-Boutigue, M.-H.; Frisch, B.; Schaaf, P.; Ihiawakrim, D.; et al. Mimicking the chemistry of natural eumelanin synthesis: The KE sequence in polypeptides and in proteins allows for a specific control of nanosized functional polydopamine formation. Biomacromolecules 2018, 19, 3693?3704. [2] El Yakhlifi, S.; Ihiawakrim, D.; Ersen, O.; Ball, V. Enzymatically Active Polydopamine @ Alkaline Phosphatase Nanoparticles Produced by NaIO4 Oxidation of Dopamine. Biomimetics 2018, 3, 36S

10:15 Coffee break    
11:15 Plenary Session 2    
12:30 Lunch    
Nanostructured surfaces for tissue and cell control II : Silvia Giordani
Authors : Matthew Ryen Lockett
Affiliations : Department of Chemistry, University of North Carolina at Chapel Hill

Resume : In tissues, gradients of oxygen and nutrients extend radially from blood vessels. The steepness of these gradients increase significantly when a blood vessel is occluded, or in the case of the tumors when the rate of proliferation outpaces the rate of vascularization. The extent of hypoxia in tumors has been correlated with cancer aggressiveness, drug resistance, and invasiveness. Despite the pivotal role that the extracellular environment plays in tumor biology, there are a limited number of in vitro assays able to quantify cellular morphology, gene- and protein-expression, or drug sensitivities in well-defined oxygen or nutrient gradients. This presentation will discuss two applications of our recent efforts to develop 3D co-culture models of healthy and tumorigenic breast tissues. These cultures utilize paper scaffolds as supports; can be assembled into tissue-like architectures; are readily prepared in 96-culture formats that are amenable to screening in traditional well plate readers. In the first application, I will show the importance of co-culture formats when predicting the in vivo potency of endocrine disrupting chemicals. This example will highlight our efforts to not only prepare a more representative screening platform but also to develop technologies to monitor intercellular signaling in 3D cultures in real-time. In the second application, I will show that abiotic gradients in the microenvironment play a critical role in modulating estrogen sensitivity. This example will highlight our efforts to quantify the spatial and temporal formation of gradients in our 3D cultures and relate those gradients to cellular responses.

Authors : Tolou Shokuhfar, Reza Shahbazian
Affiliations : University of Illinois at Chicago

Resume : Engineered-nanotubular structures offer exciting progress toward the design of multifunctional medical implants. Using facile electrochemical technique based on low cost electrode materials, we have been able to fabricate three-dimensional high quality self-aligned nanotubes on the surface of arbitrary geometries. Biocompatibility studies were conducted with MG-63 and human mesenchymal stem cells (hMSCs) through MTT assay. Furthermore, cell morphology and cytoskeleton organization were observed by SEM and laser scanning confocal microscopy (LSCM). The osteoblastic differentiation capacity of hMSCs was studied by real-time PCR, as well as their angiogenesis ability by measuring the total release of vascular endothelial growth factor (VEGF). Finally, viability of Staphylococcus aureus (S. aureus) was assessed by live/dead bacterial viability assay. Results show that bio-functionalized TiO2 nanotubular surfaces are biocompatible and modulated cell morphology. Such novel bio-selective implant surfaces are able to improve osseointegration and avoid infection simultaneously. In addition they can prevent unnecessary side effects caused by oral administration of drugs, increase drug efficiency, and prevent infection related implant complications and failures.

Authors : Jooken S. 1, Deschaume O. 1, Krylychkina O. 2, de Coene Y. 1, Callewaert G. 3, Bartic C. 1
Affiliations : 1) Laboratory of Soft Matter and Biophysics, Department of Physics and Astronomy, KU Leuven, 3001 Leuven, Belgium. 2) Department of Life Science Technologies, IMEC, 3001 Leuven, Belgium 3) Department of Cellular and Molecular Medicine, KU Leuven Campus Kulak, 8500 Kortrijk, Belgium

Resume : In the field of cardiac tissue engineering the incorporation of metal nanomaterials into artificial extracellular matrices has led to improved functioning of engineered cardiac patches through enhanced mechanical and electrical properties [1]. Moreover, the environment-sensitive electrical, magnetic or optical properties of nanoparticles can potentially be used to monitor the proper, native-like functioning of the tissue construct. In this work, we developed nanofibrillar cellular matrices where semiconductor nanocrystals (quantum dots, QDs) are attached onto collagen fibers for in situ, optical monitoring of cardiomyocyte activity. Collagen, abondantly present in natural extracellular matrices, displays multiple cell binding motives and therefore enhances QD localization in respect to the cell membrane. On the other hand, the optical properties of QDs are modulated by cellular responses (like membrane electric fields or mechanical deformation) and can therefore be used for in situ cellular monitoring. We demontrate optical readout of the activity of primary rat cardiomyocytes cultured on top of such hybrid matrices by the QD two-photon fluorescence . Cardiomyocytes cultured on hybrid scaffolds display satifactory cell viability compared to control substrates and the method can easily be extended to 3D tissue constructs for future applications. [1] Kankala, R. K. et al., ACS Biomaterials Science and Engineering. 2018.

Authors : Sungrok Wang, Dong-Hee Kang, Myung-Han Yoon*
Affiliations : School of Materials Science & Engineering Gwangju Institute of Science & Technology; School of Materials Science & Engineering Gwangju Institute of Science & Technology; School of Materials Science & Engineering Gwangju Institute of Science & Technology

Resume : Electrospun solid fibers have been utilized as porous scaffolds for a variety of three-dimensional (3-D) cell cultures but there still exist practical issues such as low optical transparency, unfavorable mechanical stiffness, poor dimension controllability, etc. In this research, we developed natural polymer-based colloidal hydrogel fibers (e.g. gelatin fibers) with positive or negative charges. The resultant colloidal fibers exhibited excellent biodegradability, high optical transparency, controllable mechanical properties, and stable dispersion in water. Subsequently, the electrostatic interaction was introduced between positively- and negatively-charged colloidal fibers, leading to the entangled hydrogel fiber network with microscale porosity. Furthermore, it was demonstrated that charge density, overall diameter, and swelling ratio of colloidal hydrogel fiber can be easily modulated to optimize these novel hydrogel scaffolds suitable for various types of 3-D cell cultures.

Authors : M. J. Lüther, K. Brassat, J. K. N. Lindner
Affiliations : Nanostructuring, Nanoanalysis and Photonic Materials group, Dept. of Physics, Paderborn University, Germany; Center for Optoelectronics and Photonics Paderborn CeOPP, Paderborn, Germany

Resume : The controlled immobilization of functional bio- or inorganic nanoparticles (NPs) on nanopatterned substrates is a highly flexible way to render tailored surface characteristics for smart biointerfaces: protein arrays can create functional hot spots guiding cell response, while arrays of metallic nanoparticles with plasmonic properties can be applied in biosensing. For the creation of such NP arrays, a fundamental understanding of colloid-solid interactions and deposition processes is, however, indispensable. We apply self-assembly techniques to design highly ordered large-area nanoobject arrays on nanopatterned surfaces. We employ block copolymer lithography for the patterning of glass, silicon or titanium surfaces with sub-20 nm features to tailor the surface morphology, i.e. topography and local surface chemistry. Particularly, we present arrays of nanopores with a diameter of 17 nm, which we then use as templates for the deposition of NPs. We exploit convective self-assembly to deposit NPs with diameters of 5-14 nm selectively inside nanopores and create ordered arrays with a pattern density of 10^11 cm^-2. In particular, we use Au NPs as model system and ferritin NPs as bio-NPs. Thus our findings can be transferred to various material systems and elucidate solid-bio interactions. We investigate the colloid-solid interactions by measurements of surface and particle zeta potentials as well as surface wettabilities and analyse the NP arrays by SEM, AFM and TEM.

15:30 Coffee break    
Nanomaterials for biosensing and biodelivery III : Seiya Tsujimura
Authors : Gemma-Louise Davies
Affiliations : Department of Chemistry, University College London (UCL), United Kingdom

Resume : Paramagnetic chelates have seen application in a number of fields and are well known for their roles in medicine, particularly in enhancing the potency of the powerful non-invasive imaging technique magnetic resonance imaging (MRI). Research towards the design of high performing and functional MRI contrast agents based on paramagnetic chelates has advanced enormously in recent years. In particular, the exploitation of nanoscale carriers has expanded the toolkit of this imaging technique, facilitating targeting and the potential for diagnostic as well as therapeutic delivery agents. Responsive MRI contrast agents, which can provide accurate disease diagnosis through a change in image contrast triggered by a specific stimulus or biochemical variable, represent the next milestone in non-invasive disease diagnosis and management. In this talk, I will describe our efforts towards optimizing the design of nanoscale contrast agents which can provide high signal contrast at exceptionally low doses. I will further describe our latest research into ?switchable? imaging contrast from a modified mesoporous silica nanoparticle scaffold doped with gadolinium-chelates (Gd-MSNs) and externally grafted with a thermoresponsive polymer (polymer-Gd-MSNs). These particles exploit a selective environmental response which is capable of localizing strong MRI signal at the stimulus site, providing a clear and identifiable site identification (and hence potential diagnosis). This proof-of-concept work is of significant value in the emerging field of diagnostic MRI.

Authors : Stephen J. Devereux, Mona Khan, Marina Massaro, Andrew Barker, David T. Hinds, Badriah Hifni, Jonathan A. Coulter, Jeremy C. Simpson and Susan J. Quinn.
Affiliations : School of Chemistry, University College Dublin, Belfield, Dublin 4, Ireland; School of Pharmacy, Queen?s University Belfast, Belfast, BT9 7BL, UK; School of Biology & Environment Science, University College Dublin, Belfield, Dublin 4, Ireland.

Resume : Carbon nanohorns (CNH) are attractive systems for cellular imaging, diagnostics and therapeutics due to their low toxicity, high surface area, and ease of functionalisation.1,2 This work reports the use of CNHs for (i) non-covalent uptake of porphyrin drug molecules and (ii) covalent loading of gold nanoparticles. The poor cellular uptake of many porphyrins is a barrier to their application in phototherapeutic applications,2 biocompatible CNH carriers offer a means to overcome this. The binding interactions of two cationic porphyrins, PtTMPyP4 and H2TMPyP4 have shown very high affinity to oxidised carbon nanohorns through non-covalent, electrostatic interactions. Brightfield microscopy demonstrated the efficacy of sparsely loaded Porphyrin-CNH constructs to be internalised within HeLa cells, which undergo rapid cell death upon visible excitation. In the past decade, gold nanoparticles have been used in biomedical applications for sensing, drug delivery and more recently radiosensitization of resistant cancer cells.4,5 Yet they are prone to aggregation in ionic or biological environments. Immobilisation of gold nanoparticles onto ligand functionalised CNHs allows for the utilisation of their therapeutic properties, reducing the risk of aggregation. Readily dispersed, CNH supported gold nanoparticles have shown to have increased stability in buffer and cell media compared to free gold and are excellent candidates for radiosensitization. 1) S. J. Devereux, et al. Chem. Eur. J., 2018, 24, 14162-14170. 2) S. Iijima, et al. Chem. Phys. Lett. 1999, 309, 165 3) M.A. Rajora, et al. Chem. Soc. Rev., 2017, 46, 6433. 4) S. A. Belhout, et al. Chem. Commun., 2016, 52, 14388-14391 5) W. Roa, et al. Nanotechnology, 2009, 20, 375101.

Authors : Kota Nagura,1 Satoshi Shimono,1 Tsukuru Amano,2 Fumi Yoshino,2 Tatsuhisa Kato,1 Naoki Komatsu,1 Rui Tamura1
Affiliations : 1Graduate School of Human and Environmental Studies, Kyoto University, Kyoto 606-8501, JAPAN. 2Shiga University of Medical Science, JAPAN

Resume : We have prepared various all-organic magnetic soft materials containing a cyclic nitroxide radical moiety as a spin source [1]. In this talk, we report the preparation of all-organic magnetic nanoemulsions composed of the non-ionic surfactant and the hydrophobic nitroxide radical compound [2]. The properties of the nanoemulsions have been investigated by small angle neutron scattering (SANS) and dynamic light scattering (DLS) analyses, EPR spectroscopy, and MRI method. The nanoemulsions showed high colloidal stability, high reduction resistance to ascorbic acid, low cytotoxicity and an enough contrast enhancement in the proton longitudinal relaxation time (T1)-weighted MR images in (-)-PBS in vitro and in vivo. Furthermore, an additional hydrophobic anticancer drug such as Taxol® was simultaneously encapsulated inside the nanoemulsions. We expect that the drug-loaded nanoemulsions can be used as a biocompatible magnetic drug carrier for MRI-visible targeted delivery system. [1] a) Uchida, al. J. Mater. Chem. 2009, 19, 6877; b) Uchida, Y. et al. J. Am. Chem. Soc. 2010, 132, 9746; c) Takemoto, Y. et al. Soft Matter 2015, 11, 5563 [2] Nagura, K, Komatsu, N., Tamura R., at al., Chem. Eur. J., 2017, 23, 15713; Pharmaceutics, in press.

Authors : Alvaro Artiga, Francisco Ramos-Sanchez, Sonia Garcia-Embid, Ines Serrano-Sevilla, Laura De Matteis, Scott G. Mitchell, Carlos Sanchez-Somolinos and Jesús M. de la Fuente.
Affiliations : Instituto de Ciencia de Materiales de Aragon (ICMA), Consejo Superior de Investigaciones Cient?ficas (CSIC)-Universidad de Zaragoza and CIBER-BBN, C/ Pedro Cerbuna 12, 50009 Zaragoza, Spain. Instituto de Nanociencia de Aragon (INA), Universidad de Zaragoza and CIBER- BBN, C/Mariano Esquillor s/n, 50018 Zaragoza, Spain

Resume : The unique physicochemical properties of gold nanoparticles (AuNPs) make them highly applicable for drug release, optoacoustic imaging, biosensing and photothermal therapy. This work highlights new methodologies for the encapsulation of AuNPs in chitosan hydrogels in order to increase their applicability and efficacy in health-related applications. AuNPs can be employed in photothermal therapy (PTT) applications as efficient light-to-heat transducers for the selective ablation of target cells. We have compared the heating capability, cellular internalization, toxicity and thermoablation capacity of two different types of anisotropic AuNPs: gold nanorods (AuNRs) and nanoprisms (AuNPrs) [1]. Our studies have shown that both AuNPs were highly efficient photothermal converters, but AuNRs possess a more efficient heating capability. Nevertheless, in vitro thermoablation studies demonstrate that AuNRs display an extremely poor cellular internalization thereby limiting their application. To improve the PTT application of AuNRs we have entrapped them inside cell-adhesive chitosan hydrogels to produce functional nanocontainers with the ability to adhere to the cytoplasmic membranes of cells, avoiding any need for cellular internalization and thus rendering them as highly efficient PTT agents [2]. Neverhteless, one key disadvantage of this entrapment methodology is the relatively limited control of the size and size-dispersion of the nanocontainers. To improve these drawbacks we have developed a novel strategy for AuNP microencapsulation in chitosan hydrogel using a high-throughput, continuous and automatic inkjet printing. This scalable industrially relevant approach has offers a high rate of production, excellent control of the microcapsules size and high encapsulation efficiency; obtaining monodisperse chitosan microcapsules containing AuNPs. We have demonstrated that these microcapsules did not display cellular toxicity in vitro and are extremely resistant to pHs, gastric and colon simulated medium degradation. [3] For these reasons we are currently studying the use of these chitosan hydrogels for oral administration of AuNPs in vivo, analyzing their retention in the digestive tract thanks to their muco-adhesive properties and the liberation of AuNPs in the intestine and their absorption to the bloodstream of mice. References [1] Artiga, Á., Alfranca, G., Stepien, G., Moros, M., Mitchell, S. G., and de la Fuente, J. M. (2016). Nanomedicine 11, 2903?2916. doi: 10.2217/nnm-2016-0257 [2] Artiga, Á., García-Embid, S., Matteis, L. D., Mitchell, S. G., and de la Fuente, J. M. (2018). Front. Chem. doi: 10.3389/fchem.2018.00234 [3] Artiga, Á., Serrano-Sevilla, I., Matteis, L. D., Mitchell, S. G., Sánchez-Somolinos, C., and de la Fuente, J. M. (2018). Chem. Comm. (In preparation)

Authors : Yu-Hsuan Hsu, I-Hsin Jen, Ling-Chu Yang, Yun-ching Chen, Dehui Wan
Affiliations : Institute of Biomedical Engineering and Frontier Research Center on Fundamental, National Tsing Hua University, Hsinchu, 300, Taiwan

Resume : Recently, some groups reported that cancer cells might starve to death by blocking them obtain nutrition such as glucose, indicating the starving therapy is a potential way for cancer treatment. However, the hypoxia condition in tumor microenvironment may inhibit the efficacy of starving therapy. Herein, we developed a combined photothermal/starving therapy for cancer treatment. First, we synthesized Au shells (GNs, photothermal agent) and then reduced Pt on them to form GN@Pt (catalyst for H2O2 decomposition). The synthesized particles could convert the NIR light to heat the solution up to 60 ?. Then, they could efficiently catalyze the decomposition of H2O2 and thus the generated O2 concentration reached ~7 ppm in 30 min. More importantly, the GN@Pt display great thermal and chemical stability for repeated-photothermal therapy and long-term hypoxia improvement, respectively. After mixing GN@Pt, glucose oxidase (GOx) and silk fibroin solution together to form an injectable hydrogel solution (SFs/GN@Pt+GOx), we evaluated H2O2 decomposition ability and glucose oxidation ability of the composite hydrogel. Moreover, we proved the anti-cancer ability of SFs/GN@Pt+GOx in hypoxia condition in vitro. Finally, in order to confirm the efficacy in vivo, the hydrogel was orthotopically injected into mice bearing with 4T1 breast cancer and followed by laser irradiation in several days. The preliminary data shows that our method would be a potential way for breast cancer treatment.

Authors : Federica Mariani (a), Isacco Gualandi (a), Domenica Tonelli (a), Marta Tessarolo (b), Beatrice Fraboni (b), Erika Scavetta (a)
Affiliations : (a) Dipartimento di Chimica Industriale ?Toso Montanari?, Università di Bologna, Viale Risorgimento 4, 40136 Bologna, Italy. (b) Dipartimento di Fisica e Astronomia, Università di Bologna, Viale Berti Pichat 6/2, 40127 Bologna, Italy

Resume : Dopamine (DA) is known as one of the most important neurotransmitters in mammals and its detection is currently a subject of significant interest. Indeed, real-time determination of DA is crucial in the diagnosis of several neurological disorders, such as Parkinson?s disease, autism and schizophrenia. However, typical concentration values do not exceed the nM range in biological samples, where ubiquitous interfering agents, such as Uric Acid (UA) and Ascorbic Acid (AA), can be found in concentrations up to 100-1000 times higher. For these reasons, common chemical sensors do not exhibit an adequate sensitivity for in vivo applications. Differently, Organic Electrochemical Transistors (OECTs) are bioelectronic devices that have recently attracted large attention in the biomedical arena for the high provided sensitivity, together with biocompatibility and low-cost. On one hand, thanks to the intrinsic signal amplification given by the transistor configuration, the OECT could be a tool for reliable detection of dopamine in biological fluids. On the other hand, the selectivity issue must be addressed to allow its widespread use in real-life applications. In this work we explore a new approach to selectively identify and determine the contributions of different analytes, i.e. DA, UA and AA, to the OECT electrical output signal through a linear scan of the gate potential.[1] OECT sensors were entirely made of PEDOT:PSS as both channel and gate material in order to take advantage of the peculiar electrochemical properties of the conducting polymer. First, we carried out electrochemical characterisation to achieve a deeper insight into the electrochemical processes occurring at the polymeric gate electrode, showing that the oxidation of the three analytes takes place at different potentials. After that, we proposed a new potentiodynamic approach, demonstrating that the all PEDOT:PSS OECT can selectively detect the three different analytes when present in the same solution, as their oxidation occurs at different gate potentials. Finally, the signal related to each compound can be individually resolved by means of the OECT transconductance and the sensor exhibits a very sensitive linear response for all the analytes. [1] I. Gualandi, D. Tonelli, F. Mariani, E. Scavetta, M. Marzocchi and B. Fraboni, Scientific Reports, 2016, 6, 35419

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Functional biointerfaces III : Estelle Lebegue
Authors : M. Nimshi. L. Fernando 1, Dhanusha T. N. Rathnayake 1, Nilwala. Kottegoda 2, J. K. D. S. Jayanetti 1, Veranja Karunaratne 3, Dilushan. R. Jayasundara 1
Affiliations : 1.Department of Physics, University of Colombo, Sri Lanka 2.Department of Chemistry, University of Sri Jayewardenepura, Sri Lanka 3.Department of Chemistry, University of Peradeniya, Sri Lanka

Resume : Development of controlled release biomolecules by encapsulating into Nano Hydroxiapatite (HA-Np) have recently gained popularity. However, the impact of the surface morphology of HA-Np on the encapsulation mechanism of these biomolecules remain to be explored. Ureas are used in applications in medicinal chemistry as a model system for the design and optimization of various therapeutic agents. The unique hydrogen binding capabilities of ureas make them an important functional group in molecules with broad range of bioactivities. Morphologically different HA-Np thin films that specifically expose (100) and (002) planes were fabricated on the quartz crystal piezoelectric sensors. These planes mainly consists Ca and PO4-3 sites respectively. Electrophoretic deposition and spin coating techniques were used without high temperature sintering for HA-Np sensor fabrication. Urea adsorption onto both Ca and PO4-3 sites were monitored, in the PBS buffer, in-situ and in real time from the quartz crystal microbalance. The above adsorption data, sigmoidal in shape, were fitted with three different sigmoidal models which include Logistic model, Weibull model and Emperical Hill model (EHM) with the latter giving the best fit for the data. Kinetic parameters derived from the fit to EHM, show that adsorption rates of urea on the Ca site is higher than that onto the PO4-3 site. Moreover the affinity of urea to multiple binding sites of HA-Np leads to Cooperative binding. Modelling information shows that the cooperative parameter of the Ca site is also higher than the PO4-3 site. Kinetic and cooperative parameters reveal that the Ca site of HA-Np is more favourable as a functional coating in sensing applications and in development of controlled release drugs and fertilizers.

Authors : Lorena Maria Cucci1,2, Giusy Villaggio1, Diego La Mendola2,3, Cristina Satriano1,2
Affiliations : 1Department of Chemical Sciences, University of Catania, Italy; 2Consorzio Interuniversitario di Ricerca in Chimica dei Metalli nei Sistemi Biologici (C.I.R.C.M.S.B.), Italy; 3Department of Pharmacy, University of Pisa, Italy.

Resume : Angiogenin (ANG), involved in most stages of the angiogenesis process, has been shown related to many pathophysiological processes, including tumorigenesis, neuroprotection, inflammation and regeneration of damaged tissues [1]. In this work, we investigated a hybrid made of ANG assembled to gold nanoparticles and graphene oxide nanosheets, to exploit the synergic effects of antioxidant AuNP [2] and antimicrobial GO [3], respectively. Au-GO-ANG were characterized by UV-visible spectroscopy, to correlate the changes in the plasmonic peak as well as in the π*-π transitions to the protein interaction with Au and GO, respectively. AFM and DLS measurements confirmed the strong association of the protein both to the nanoparticles and to the nanosheets. Lipid lateral diffusion and viscoelastic changes measured by FRAP and QCM-D within supported lipid bilayers pointed to a strong interaction of the nanocomposites with the model cell membranes. The developed systems promoted fibroblasts migration and wound closure, and cell viability assays showed low cytotoxicity. Confocal microscopy cell imaging evidenced dynamic processes at the level of cytoskeleton and sub-cellular compartments. References 1. Sheng et al., AABS, (2016) 48, 399. 2. Di Pietro et al., Curr Top Med Chem (2016) 16, 3069. 3. Mangadlao et al., Chem Commun (2015) 51, 2886.

Authors : E. K. Oikonomou 1*, L. Ferreira 2, M. Bacovic 1, F. Mousseau 1, M. Ould Ali 3, A.-A. Arteni 3, M. Caroso 2 and J.-F. Berret 1
Affiliations : 1 Matière et Systèmes Complexes, UMR 7057 CNRS Université Denis Diderot Paris-VII, Bâtiment Condorcet, 10 rue Alice Domon et Léonie Duquet, 75205 Paris, France; 2 Laboratorio Nacional de Nanotecnologia (LNNano), Centro Nacional de Pesquisa em Energia e Materiais (CNPEM), CEP 13083-970, Campinas, Sao Paulo, Brasil; 3 Cryo Microscopy Platform, Institute for Integrative Biology of the Cell (I2BC), CEA, CNRS, University Paris South, University Paris-Saclay, Gif-sur-Yvette, France

Resume : Numerous therapeutic nanocarriers have been developed during the last decade. For nanomedicine, nanomaterials need to be coated to prevent protein adsorption and hepatic capture. Here, we examine the formation of supported lipid bilayer (SLB) on spherical nanoparticles as an alternative coating strategy. Negative and positive silica nanoparticles (diameter 50 to 100 nm) were studied in conjunction with synthetic (POPG, DOPC) and biological (Curosurf®, a pulmonary surfactant) lipids. Herein we demonstrate that contrary to recent literature reports, mixing particles and surfactant vesicles does not lead to spontaneous SLB formation. With oppositely charged species, aggregation is obtained. Applying in situ mechanical energy to mixed aggregates helps however reshaping the lamelarity through dispruption and reformation of the assembled structures, yielding to well-defined SLBs. The SLB formation was confirmed using cryogenic transmission electron microscopy. The stability of these structures in biological fluids in presence of proteins was finally demonstrated.

Authors : T. Flinois [1], E. Lebègue [1], A. Zebda [2], J. P. Alcaraz [2], D. Martin [2], F. Barrière [1]
Affiliations : [1] Univ Rennes, CNRS, Institut des Sciences Chimiques de Rennes, France [2] Univ Grenoble Alpes, CNRS, TIMC- IMAG, Grenoble, France

Resume : The complexity of biological membranes has motivated the development of models that can be supported on solids and electrodes. However, supported lipid bilayers often display poor stability in time [1]. In order to study the transmembrane antiporter NhaA protein [2] [3], we have developed an original approach aimed at increasing the stability of the lipid layer supported on an electrode thanks to electrografting. The cathodic reduction of aryl diazonium salts [4] generated in situ from 4-decylaniline (4DA) makes it possible to fix mixed vesicles (4DA and lipids) on the electrode surface. The grafted liposomes then break up and fuse to form supported lipid layers. Quartz microbalance studies with viscoelasticity measurements have been carried out to follow the fusion of mixed vesicles and to optimize the pH and salinity conditions. The stability of the supported lipid layer has been shown to increase from less than one day to about two weeks with the grating approach. Then, the insertion of either an active or inactive NhaA protein (a sodium / proton antiporter) in the supported lipid layer has been carried out by fusion of proteoliposomes [5]. This has been followed by cyclic voltammetry and electrochemical impedance spectroscopy onto an electrode modified by an adsorbed pH sensor (2-anthraquinonesulfonate) [6]. [1] D. W. Jeong, et al., Nature Scientific Report. 2016, 6, 38158-38165 [2] D. K. Martin et al., “Liposomes, Lipid Bilayers and Model Membranes: From Basic Research to Application” eds: Pabst G, Kucerka N, Nieh MP, Katsaras J. CRC Press, Taylor & Francis Group, 2013 [3] Project bioWATTs-ANR-15-CE05-0003 [4] D. Bélanger, J. Pinson, Chemical Society Reviews, 2011, 40, 3995-4048 [5] G. J. Hardy et al., Current Opinion in Colloid & Interface Science, 2013, 18, 448–458 [6] C. Batchelor-McAuley et al., The Journal of Physical Chemistry B, 2010, 114, 4094–4100

10:00 Coffee break    
Functional biointerfaces IV : Alessandro Iannaci
Authors : Colm Delaney 1, Larisa Florea 2, Niamh Geoghegan 1, Susan M. Kelleher 1
Affiliations : 1 School of Chemistry, University College Dublin, Dublin 4, Ireland 2 School of Chemistry, Trinity College Dublin, Dublin 2, Ireland

Resume : To date, 2 photon-polymerisation (2PP) has proven an effective micro/nanofabrication tool for the realisation of high-resolution structures from UV-curable photoresists. Exploiting commercially available resins such as SU-8, Ormocomp, and IPL has yielded structures with features smaller than 100 nm.[1] There exists a challenge for the materials chemist to develop a means of adaptability which will enable extension of this impressive tool to encompass biocompatible smart polymers, either via direct printing of nanoscale structures, or via replica moulding from 2PP generated patterns.[2,3] In this work we present the generation of 2D and 3D micro- and nano-sized structures fabricated from optimised cocktails of biocompatible monomers. The use of 2PP-produced structures as replica moulding masters will also be presented. The ability to cast high-fidelity mm-sized arrays from a wide range of materials, while retaining the nanostructure, will be demonstrated. Characterisation of these millimetre arrays using SEM, AFM, and Confocal Microscopy showcases the potential of this approach as a novel means of generating high-resolution nanostructures for use at the biological-surface interface.[4] [1] Appl. Phys. Lett. 90 (2007) 71106. [2] Sci. Rep. 8 (2018) 564. [3] Polym. Adv. Technol. 23 (2012) 992–1001. [4] Sci. Rep. 7 (2017) 9247.

Authors : Andrey Sviridov, Ulyana Natashina, Maxim Gongalsky, Andrey Kudryavtsev, Valery Andreev, Liubov Osminkina
Affiliations : M.V. Lomonosov Moscow State University; M.V. Lomonosov Moscow State University; M.V. Lomonosov Moscow State University; Institute of Theoretical and Experimental Biophysics, Russian Academy of Sciences; M.V. Lomonosov Moscow State University; M.V. Lomonosov Moscow State University

Resume : Nanoparticles based on porous silicon attract a lot of interest because of the outstanding properties of biocompatibility and biodegradability in the living environment. Wide opportunities of the surface modification, as well as efficient photoluminescence in the visible and infrared range, make them perfect agents for various theranostic applications, including targeted delivery of chemotherapeutic drugs. The current study is devoted to both theoretical and experimental investigation of sonoactivation of drug-loaded mesoporous silicon nanoparticles coated by biopolymers with the MHz-range ultrasound of moderate intensity. The role of two fundamental effects – acoustic cavitation and ultrasound-induced heat deposition – is taken into account. The presence of solid porous nanoparticles lowers the cavitation threshold in aqueous media due to the growth of air bubbles from nuclei and also leads to the heating of surrounding area due to the ultrasound energy absorption. In vitro experiments reveal the significant inhibition of cancer cell proliferation under the combined exposure to the nanoparticles and ultrasound radiation as compared to the intact group of cells. Investigation of the above physical effects at the nanoparticle/ bioenvironment interface has a great potential for the development of new strategies for the controlled drug release.

Authors : Sonia García-Embid, Francesca Di Renzo, Laura De Matteis, Nicoletta Spreti, Jesús M. de la Fuente
Affiliations : Instituto de Ciencia de Materiales de Aragón (ICMA), CSIC - Universidad de Zaragoza, Zaragoza, Spain and CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain; Department of Physical and Chemical Sciences, University of L’Aquila, L’Aquila, Italy; Instituto de Nanociencia de Aragón (INA), Universidad de Zaragoza, Zaragoza, Spain and CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain; Department of Physical and Chemical Sciences, University of L’Aquila, L’Aquila, Italy; Instituto de Ciencia de Materiales de Aragón (ICMA), CSIC - Universidad de Zaragoza, Zaragoza, Spain and CIBER-BBN, Instituto de Salud Carlos III, Madrid, Spain;

Resume : The World Commission on Environment and Development introduced the term sustainable development, indicating the present need of modern industrial processes to optimize the use of raw materials, reduce waste and avoid the use of toxic molecules. Amongst the approaches used over the years to achieve this sustainability, biocatalysts, especially enzymes, have been in the spotlight due to their great properties. Sustainability of enzymatic catalysis is maintained through the whole cycle: from their production (living organisms) to the waste treatment.[1] However, their present application at industrial scale is hampered by the high costs in their production that decrease cost-effectiveness of their application. Reutilization of the enzyme is therefore the tool to obtain more cost-effective and sustainable industrial processes. Immobilization of these biocatalysts allows an easy recovery of the material and protection from the reaction conditions in the different production steps.[2] Nowadays, nanotechnology offers one of the most forefront approaches for enzyme immobilization. Magnetic nanoparticles allow an easy recovery of an immobilized enzyme using a simple magnet to separate the catalyst from the reaction product. To improve colloidal stability of the support, reduce interactions between the magnetic cores and prevent interactions with the environment that can affect both support and enzyme stability, a polymer coating is an easy and cheap approach.[3] Using this approach, in this work we developed a hybrid, modular micro-support based on organic and inorganic nanocomponents. The easiness of tuning the composition of the support makes this system a potentially universal support for the immobilization of very different catalytic systems. Here we present the application of the developed micro-support for the immobilization of chloroperoxidase (CPO), an enzyme able to catalyze many reactions of large-scale interest. A multipolysaccharidic shell containing the immobilized enzyme and obtained through a combination of chitosan and alginate, biodegradable polymers from natural sources, was used to stabilize a nanoemulsion core in which magnetic nanoparticles were embedded. Microsupports obtained through different combinations of nanocomponents were characterized and tested in terms of their chemical stability under reaction conditions. An excellent reusability of the entrapped enzyme was observed opening the way to the immobilization of different catalytic systems and to the scale-up study in view of future industrial application.[4] References [1] R.A. Sheldon, J.M. Woodley, Chem. Rev. 118 (2018) 801–838. [2] M.L.E. Gutarra, L.S.M. Miranda, R.O.M.A. de Souza, in:, Org. Synth. Using Biocatal., Elsevier, 2016, pp. 99–126. [3] J. Xu, J. Sun, Y. Wang, J. Sheng, F. Wang, M. Sun, Molecules 19 (2014) 11465–11486. [4] S. García-Embid, F. Di Renzo, L. De Matteis, N. Spreti, J. M. de la Fuente, Appl. Catal. A Gen. 560 (2018) 94–102.

Authors : Estelle Lebègue, Nazua L. Costa, Bruno M. Fonseca, Ricardo O. Louro, Frédéric Barrière
Affiliations : Estelle Lebègue, Nazua L. Costa, Frédéric Barrière: Univ Rennes, CNRS, Institut des Sciences Chimiques de Rennes - UMR 6226, F-35000 Rennes, France; Bruno M. Fonseca, Ricardo O. Louro: Universidade NOVA de Lisboa, Instituto de Tecnologia Química e Biológica, António Xavier, 2780-157 Oeiras, Portugal

Resume : The electrochemical detection of a pH-dependent redox protein from electroactive bacteria at an electrode modified to act additionally as an efficient pH sensor based on a redox readout is demonstrated. The pH sensing electrode was previously designed and showed to allow the immobilization and study of pH-independent and redox active cytochrome c. Here we extend this work to flavocytochrome c3, a tetraheme FAD-containing periplasmic flavoenzyme isolated from the bacterium Shewanella putrefaciens, taken as a model pH-dependent redox protein from electroactive bacteria. The modification of the electrode surface with the pH sensing modifier (catechol) stems from our previous experience in the tailoring of bio-interfaces of carbon electrodes with covalent electrografting. Flavocytochrome c3 adsorption onto the modified electrode surface is successfully achieved by cyclic voltammetry in a flavocytochrome c3 solution containing polymyxin as co-adsorbate. The electrochemical activity of the immobilized flavocytochrome c3 is detected without alteration of its native structure and by keeping intact its electrochemical properties and its catalytic fumarate reductase activity. The redox activity of the protein arises from its FAD and four hemes cofactors. The experiments evidence that the hemes’ redox potentials of flavocytochrome c3 from Shewanella putrefaciens, for which no crystal structure is yet available, depend on pH which is at variance with data from the other strains.

Authors : Nagappanpillai ADARSH, Pichandi ASHOKKUMAR, Andrey S. KLYMCHENKO
Affiliations : Laboratory of Bioimaging and Pathologies, UMR 7021 CNRS, Faculty of Pharmacy, University of Strasbourg, 67401 Illkirch, France

Resume : Optical sensing of molecular oxygen has attracted a great deal of scientific attention since the determination of oxygen concentration is essential in diverse areas, ranging from life sciences to environmental sciences [1]. Fluorescent polymer nanoparticles (NPs) have received great attention due to their exceptional brightness, color tuning, potential biodegradability and low toxicity [2]. Herein, we demonstrate a simple approach for the FRET based ratiometric detection of dissolved oxygen (DO) gradients in live cancer cells using ultrabright polymeric nanoparticles. These nanoprobes are composed of dye-loaded PMMA-MA NPs, having the diameter of 40 nm. These polymeric nanoantennas can harvest energy from hundreds of donor dyes to a single acceptor, leading to the amplification of acceptor emission, which enables the detection at the single particle level. Here, the cyanine donors efficiently transfer their excitation energy to the porphyrin acceptor, whereas the acceptor phosphorescence is quenched by the presence of DO due to triplet-triplet energy transfer. The recovery of the acceptor phosphorescence occurs by varying the oxygen concentration in the mixture from 0 to 95%, which facilitates the ratiometric detection. The fabrication of a simple microfluidic prototype provides the stable cellular oxygen gradients, which permit the ratiometric imaging of hypoxic regions in tumor cells using wide-field fluorescence microscopy. [1] P. Carmeliet et al. Nature 1998, 394, 485-490. [2] K. Trofymchuk et al. Nat. Photonics 2017, 11, 657-663.

Authors : Seung Ah Byeon, Oh Seok Kwon*
Affiliations : Infectious Disease Research Center, Korea Research Institute of Bioscience and Biotechnology (KRIBB)

Resume : The dopamine plays a crucial role as a neurotransmitter for interneuronal communication in the brain, serious diseases such as Parkinson’s disease and Alzheimer’s disease be known to the effect of dopamine dysfunction. The conventional sensors for dopamine detection have been developed with various methods and one of them is field-effect transistor (FET) using conducting nanomaterials. Herein, we developed the portable and reusable FET device, the channel of the FET sensor was consisted multidimensional carboxylated poly(3,4-ethylenedioxythiophene) nanofibers, as we called a multidimensional conducting polymer nanofibers (MCPNFs). The MCPNFs via FET system rapidly measured various dopamine concentrations and showed high-selectivity and sensitivity (100 fM) in real-time. Based on those results, the MCPNF FET sensor can provide a practical methodology for obtaining a high-performance neurotransmitter detector.


Symposium organizers
Frédéric BARRIEREUniversité de Rennes 1

Institut des Sciences Chimiques de Rennes, Campus de Beaulieu, 35042 Rennes, France

+33 2 23 23 59 43
Giovanni MARLETTAUniversity of Catania

Laboratory for Molecular Surfaces and Nanotechnology V.le A.Doria 6 Catania Italy

+39 95 7385130
Mathieu ETIENNEUniversité de Lorraine

Laboratoire de Chimie Physique et Microbiologie pour les Matériaux et l'Environnement, CNRS - LCPME, 405, rue de Vandoeuvre, F-54600 Villers-lès-Nancy, France

+33 3 72 74 73 82
Paula COLAVITATrinity College Dublin

School of Chemistry, College Green, Dublin 2, Ireland