Bioinspired and Biointegrated Materials as New Frontiers Nanomaterials IX

Resume : The basic building blocks of every neural network are neurons and their inter-cellular connections, called synapses. In nature, synapses play a crucial role in learning and memory, since they are plastic, which means that they change their state depending on the neural activity of the respectively coupled neurons. In neuromorphic systems, the functionality of neurons and synapses is emulated in hardware systems by employing very-large-scale integration technology. In this context, it seems rather natural to use non-volatile memory technology to mimic synaptic functionality. In particular, memristive devices are promising candidates for neuromorphic computing, since they allow one to emulate synaptic functionalities in a detailed way with a significantly reduced power usage and a high packing density. This tutorial aims to provide insight on current investigations in the field to address the following fundamental questions: How can functionalities of synapses be emulated with memristive devices? What are the basic requirements to realize artificial inorganic neurons and synapses? Which material systems and device structures can be used for this purpose? And how can cellular synaptic functionality be used in networks for neuromorphic computing? Even if those questions are part of current research and not yet answered in detail, our aim is to present concepts that address those questions.

Resume : The complex analysis based tasks such as computing large-scale of data, image recognition, and artificial intelligence among many others has put forward the need for neuromorphic computing. The Neuromorphic computing is human brain inspired efficient computation technique which demands fast switching, low power consuming and highly scalable integrated memory devices. The Resistive Random Access memory (RRAM) devices aim to fulfill the above mentioned requisite. These devices store the memory in the form of tunable resistance and are progressively used as an artificial synapse in neuromorphic circuits [1]. Most recently, the filamentary based RRAM devices were used for pattern recognition technique [2]. Although, RRAM has a wide range of application starting from emerging non-volatile memory to an artificial synapse in neuromorphic circuits, the device-to-device and cycle-to-cycle variabilities of the devices still remain a challenge [3]. The RRAM cell generally consists of a 1T-1R structure where the transistor is connected in series to the Metal-Insulator-Metal (MIM) module which is fabricated in the BEOL CMOS process. Many techniques were used in the past to protect the MIM module from subsequently applied process steps involved in the fabrication [4]. In this work, we demonstrate the role of Reactive-ion-etching (RIE) in the fabrication of MIM module. The optimized etch processes are demonstrated in the TiN/Ti/HfO2/TiN stack using spacers and encapsulation techniques. The MIM stack without the transistor is integrated into the BEOL of the 250 nm CMOS technology at IHP. An improved MIM stack etch process reduces the side wall damage of the devices, exhibits low leakage current, less variability and enhance reliability of the device performance. The switching operation was tested by means of DC voltage sweeps on the MIM RRAM devices which includes, forming, reset and set steps followed by 50 cycles of reset and set processes. References 1) A. Stefano, S. Balatti, V. Milo, R. Carboni, Z.Q. Wang, A. Calderoni, N. Ramaswamy, and D. Ielmini. "Neuromorphic learning and recognition with one-transistor-one-resistor synapses and bistable metal oxide RRAM", IEEE Transactions on Electron Devices, Vol. 63, Issue: 4, pp 1508-1515 (2016) 2) Ch. Wenger, F. Zahari, M. K. Mahadevaiah, E. Perez, I. Beckers, H. Kohlstedt, and M. Ziegler, “Inherent stochastic learning in CMOS integrated HfO2 arrays for neuromorphic computing” IEEE Electron Device Letters, Vol. 40, Issue: 4, pp 639-642 (2019) 3) E. Pérez, A. Grossi, C. Zambelli, M. K. Mahadevaiah, P. Olivo, and Ch. Wenger, “Temperature impact and programming algorithm for RRAM based memories”, in MTT-S International Microwave Workshop Series on Advanced Materials and Processes for RF and THz Applications (IMWS-AMP), 2018 IEEE, pp. 1-3 4) Y.S. Chen, H.Y. Lee, P.S. Chen, P.Y. Gu, W.H. Liu, W.S. Chen, Y.Y. Hsu, C.H. Tsai, F. Chen, M.J. Tsai, and C. Lien, “Good Endurance and Memory Window for Ti/HfOx Pillar RRAM at 50-nm Scale by Optimal Encapsulation Layer” Electron Device Letters, Vol. 32, Issue: 3, pp 390-392 (2011)

Resume : Neuromorphic systems are highly investigated in the recent past to realize novel bio-inspired computing architectures which may have advantages in power dissipation and scalability over traditional transistor technologies. Memristive devices are promising candidates to emulate synaptic behavior of neuronal networks in hardware. Here, two different devices are used to realize pattern recognition tasks in hardware, i.e. interface-based double barrier memristive devices (DBMD) and filament-based resistive random access memory devices (RRAM). The former are analogue switching devices integrated in a selector-less crossbar array. An unsupervised Hebbian learning scheme was used for the pattern recognition task. The latter devices are fully CMOS integrated 1-transistor-1-resistor (1T1R) cells which act as binary switches. Here, a novel learning scheme utilizing the inherent switching probability has been used. Both networks were built with hardware devices and software neurons. It is shown that both types of memristive devices can be used as artificial synapses in neuromorphic circuits. (http://www.for2093.uni-kiel.de/en?set_language=en)

Resume : One of the latest trends in the fields of tissue engineering as well as oncological research is the development of in vitro 3D systems mimicking the target tissue or organ. Indeed, there is an increasing demand for in vitro models recapitulating the tridimensional structure and microenvironment experienced by cells in vivo. This approach has manifold applications in fields such as basic research, drug discovery, tissue engineering, offering a valid alternative to the use of animals in testing. Interestingly, certain tissues are known to be regulated by endogenous bioelectrical cues, in addition to chemical and mechanical cues. One such tissue is bone. Moreover, electrical stimulation has been proven to support cell proliferation as well as to boost the expression of genes related to stem cells osteogenic differentiation. We report on the development of electroactive scaffolds based on the conducting polymer PEDOT:PSS. Blends of PEDOT:PSS and Collagen type 1 were used to prepare macroporous scaffolds. These macroporous substrates were used for stem cell culture and osteogenic differentiation. First experiments of stem cell differentiation via electrical stimulation were run and some preliminary results will be discussed. Porous conductive scaffolds are a valuable in vitro platform for the development of 3D models for the study of stem cells response to electrical stimulation for bone tissue engineering.

Resume : Metal oxide nanoparticles were synthesized using an eco-friendly, simple and cost effective green synthesis method mediated by green extracts of Moringa Oleifera, Aspalathus Linearis, Sageretia Thea, Maize (Zea mays L.). The Metal oxides nanoparticles were thermally oxidized to pure metal oxide nanoparticles at temperature between 100 to 1000 °C. The phases of the metal oxides were confirmed by X-ray diffraction (XRD) studies. The values of the bandgap energies were determined from diffuse reflectance of the nanoparticles unannealed and annealed metal oxide nanoparticles. The morphology and structure of the metal oxides was determined by high resolution transmission electron microscopy (HRTEM), high resolution scanning electron microscopy (HRSEM) and Fourier-transform infrared spectroscopy (FTIR). The electrochemical properties were studied using cyclic voltammetry (CV), Square Wave Voltammetry (SWV) galvanostatic charge discharge (GCD) cycles and electrochemical impedance spectroscopy (EIS).

Resume : The design and synthesis of materials with useful, novel properties is one of the most active areas of contemporary science, generating a veritable explosion of scientific activity in areas such as biomaterials, cell and tissue engineering, organic photovoltaics and light-emitting materials, and nanomaterials for a myriad of medical and nonmedical applications. This new era of materials design and discovery covers many disciplines from chemistry and biology to physics and engineering. Conventionally, it takes at least 20 years to move a material from initial discovery to the marketplace. To accelerate the pace of novel materials discovery, computational methods such as artificial intelligent machine learning techniques can be used to construct predictive materials property models and allow rapid scanning of large chemical datasets to systematically identify attractive candidates for specific applications. This presentation will showcase recent studies on data-driven design of functional materials for a broad spectrum of applications such as drug delivery, and antifouling materials.

Resume : Protein and nucleic acids in nature typically self-assemble into interesting structures intimately related to their function. The ability to use these materials to go beyond nature and design and build functional artificial structures is of great interest and could be classified as a ?structural synthetic biology? branch of bionanoscience. The attractiveness of this approach is twofold: Firstly, in building artificial complexes we may gain some understanding of the rules and processes controlling the formation and function of naturally occurring biological machines. Secondly, if we can design and build artificial bionano structures we may be able to impart novel functionality that is useful for production of new materials or new therapeutics/delivery agents. Here I will overview some of the work in the field including our own work in producing such structures from DNA (using the DNA origami technique)[1, 2] and protein including our recent work on artificial protein cages with unusual geometry and stability, held together with gold atoms.[3, 4] 1. Godonoga, M., et al., A DNA aptamer recognizing a malaria protein biomarker can function as part of a DNA origami assembly. Sci. Rep., 2016. 6. 2. Tang, M.S., et al., An aptamer-enabled DNA nanobox for protein sensing. Nanomed-Nanotechnol, 2018. 14(4): p. 1161-1168. 3. Malay, A.D., et al., Gold Nanoparticle-Induced Formation of Artificial Protein Capsids. Nano Lett., 2012. 12: p. 2056-2059. 4. Imamura, M., et al., Probing structural dynamics of an artificial protein cage using high-speed atomic force microscopy. Nano Lett., 2015. 15(2): p. 1331-5.

Resume : The talk will focus on fundamental questions regarding aspects of 1) local DNA dynamics that modulate sequence-dependent protein binding and 2) large-scale DNA conformational changes, focusing on examples from viral DNA injection machinery. I will showcase the use of novel computational modeling methods that straddle atomic-detailed molecular dynamics and elastic continuum. The computational models will expose details of the highly dynamic genetic transactions by advancing methods that access longer time and space scales and with greater detail than regular molecular dynamics simulations can. Using the elastic continuum model I will also present how one can understand and design nano-machines that inject molecules through membranes.

Resume : DNA nanotechnology is a bottom-up nanotechnology taking advantage of DNA as either a biologically or synthetically produced polymer with self-assembling properties. The DNA origami methodology [1] folds a single-stranded phage DNA (scaffold) via hundreds of synthesised oligo DNAs (staples). It offers the feasible assembly of arbitrarily addressable structures at a size of around a hundred nanometres. Using this method, a number of encapsulating structures have been produced to date including a nanoscale box with controllable lid [2], a clamshell shaped nanorobot able to expose cargo in response to target signal [3] and a nanovault aiming to cage an active enzyme [4]. However, the encapsulation capacity and cargo isolation efficiency of such structures are still limited. Here we report the design of a two component capsule-shaped DNA origami nanostructure with each component having a cavity of ca 20 x 20 x 10 nm. The design offers full accessibility to anchored cargos when the shell is open while the closed form contains a cavity of approximately 11 attolitres. We evaluated cargo accessibility and the loading capacity of the DNA origami capsule as well as its ability to protect cargo using split GFP system as proof of principle. 1. Rothemund, P. W. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297-302, doi:10.1038/nature04586 (2006). 2. Andersen, E. S. et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459, 73-76, doi:10.1038/nature07971 (2009). 3. Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831-834, doi:10.1126/science.1214081 (2012). 4. Grossi, G., Dalgaard Ebbesen Jepsen, M., Kjems, J. & Andersen, E. S. Control of enzyme reactions by a reconfigurable DNA nanovault. Nat Commun 8, 992, doi:10.1038/s41467-017-01072-8 (2017).

Resume : We fabricated a quartz crystal microbalance(QCM)-based biosensor which was utilized aptamer-attached DNA origami as a biorecognition elements and evaluated binding kinetics between alpha fetoprotein(AFP) and aptamer attached DNA origami. DNA origami was consisted of M13 scaffold DNA and numerous staple DNA [1]. It can capture a specific ligand by embedding an aptamer in its 2-D structure [1]. While QCM-based sensor has several advantages, it is difficult to detect low-molecular-weight material due to the measurement principle [2]. We considered that frequency shift on aptamer-protein interaction is improved by utilizing aptamer attached DNA origami, because biorecognition elements on the sensor surface can be increased. To assemble aptamer attached DNA origami, M13 scaffold DNA, 200 types of staple DNA and specific aptamer for AFP were mixed and annealed at 80 °C for 10 minutes. DNA origami had extended sequence to hybridize thiol modified DNA. We obtained DNA origami with a rectangle shape by using atomic force microscopy. After a gold electrode of QCM sensor chip was coated with thiol modified DNA (0.1 µM), DNA origami (0.2 nM) was immobilized on the gold electrode through the thiol modified DNA. Then, the QCM sensor was set to a QCM counter with a flow-injection system. We monitored the interaction between the molecules on the sensor surface and AFP (5 µg/ml) supplied using a flow-injection system. The frequency shift on the DNA origami coated sensor was superior to that on aptamer solely coated sensor.The result indicated that the DNA origami coated sensor had a great potential to improve the sensitivity for biosensing. [1] M. Godonoga et. al., SCIENTIFIC REPORTS, 6 (2016) 21266. [2] G. Sauerbrey, Z. Phys. 155 (1955) 206–222.

Resume : Protein cages, due to their specific structure and characteristics, can have multiple applications, such as delivery systems or nanoreactors. They are usually built from multiple copies of the same protein, which are held together by hydrophobic interactions or hydrogen bonds. Virus capsids are an examples of a natural protein cage. It is of interest to try to mimic these unique structures but control of cage assembly, morphology and symmetry is difficult. Work in the Heddle Laboratory has suggested that artificial protein cages can be assembled not by complex weak interactions but by simple gold “staples”. In detail, certain gold nanoparticles and gold(I) compounds can interact with a cysteine-containing mutant of TRAP (trp-RNA attenuation protein) to promote protein-protein bonds, which can result in production of highly stable artificial protein cage structures. Moreover, by manipulating the gold to TRAP molar ratio two sizes of protein cage can be prepared: large cage, 21-22 nm and small cage, 15-16 nm. The Cryo-EM structure of large cage has been solved, but the structure of small cage is still unknown. In this work we attempted to characterise the small cage and to build its speculative model. We now have a clearer view on the control of protein cage formation. This understanding along with mechanistic implications will be presented.

Resume : Protein cages are known to be one of the most sophisticated and robust protein self-assembled systems with wide applicability in bionanoscience. Ferritin is a typical example, it is a ubiquitous multi-subunit iron storage protein formed by 24 polypeptide chains that self-assemble into a hollow, roughly spherical protein cage with external and internal diameters of approximately 12 nm and 8 nm, respectively. Recently a new class of ferritin was discovered in archaea, which shows salt-mediated assembly properties, assembling at high salt and disassembling at low salt. We recently explored a new archeal ferritin which shows the interesting property of reversible assembly in solution, forming the canonical cage structure at high ionic strength and get disassembled in low ionic strength solution. This switchable behaviour is of note given the proven utility of ferritin as a bionano-building tool. Recently we have successfully shown that our derived ferritin can act as an excellent protein container for capturing protein cargo, and because of its reversibility, encapsulation is switchable, with cargo being released at low salt concentration. Furthermore, we found that this system has advantages over the other known salt-ferritin as it forms a complete shell around the cargo and is considerably more heat stable, as demonstrated in experiments where encapsulated enzyme retains close to full activity even at 80°C. In addition, we were also successful in making an enzyme active ferritin superlattice, and we used nano-gold as an anchor molecule for this purpose. In my presentation I will show our recent findings related to archaea ferritin and discuss their application.

Resume : Nature has developed a fascinating strategy of cryptobiosis for counteracting the stressful, and often lethal, environmental conditions. For example, certain bacteria sporulate to transform from a metabolically active, vegetative state to an ametabolic endospore state. The bacterial endospores, encased within tough biomolecular shells, withstand the extremes of harmful stressors, such as radiation, desiccation, and malnutrition, for extended periods of time and return to a vegetative state by breaking their protective shells apart when their environment becomes hospitable for living. Inspired by cryptobiosis found in nature, researchers have sought to chemically control and tailor the metabolic behaviors of non-spore-forming cells as well as enhancing their viability against adverse environmental conditions, by forming thin (< 100 nm), tough artificial shells. These living ?cell-in-shell? structures, called artificial spores, enable chemical control of cell division, protection against physical and chemical stresses, and cell-surface functionalizability, armed with exogenous properties that are not innate to the cells but are introduced chemically. The field has further advanced to the stage of chemical sporulation and germination, where cytoprotective shells are formed on living cells and broken apart on demand. The (degradable) cell-in-shell hybrids are anticipated to find their applications in various biomedical and bionanotechnological areas, such as tissue engineering, cytotherapeutics, high-throughput screening, sensors, and biocatalysis, as well as providing a versatile research platform for single-cell biology.

Resume : We suggest a cell-in-shell (or artificial spore) strategy to enhance the cell viability in the practical settings, while maintaining biological activities for therapeutic efficacy. A durable titanium oxide (TiO2) shell is formed on individual Jurkat T cells by layer-by-layer deposition of TiO2-inducing peptides and TiO2 precursor. Resulting shell protect Jurkat T cells against external heat stress. Encapsulated cells are able to stay in a state of starvation for 2 weeks, and have a resistance against high temperature. On the other hand, because of the porosity of TiO2 shell, CD3 and other antigens on cell surfaces remain accessible to the antibodies. Jurkat T cells can be stimulated with molecules or model cells (antibody-presenting microbeads) and interleukin-2 (IL-2) secretion is also not hampered by the shell formation. This work suggests a chemical toolbox for effectively preserving lymphocytes in vitro and developing the lymphocyte-based cancer immunotherapy.

Resume : Saccharides are involved in a diverse array of biological functions including cell communication, biofilm formation and inflammatory responses. Surface-bound glycans hold potential as versatile tools for tailoring the interactions of biomolecules, cells and/or organisms with solid surfaces via regulation of either specific or non-specific interactions. Therefore, there has been great interest in developing new strategies for the preparation of functional glycosylated materials, whereby glycans can be varied to play either a passive or an active role in regulating binding interactions. We have recently focused on the development of precursors and surface modification protocols for the immobilization of carbohydrates based on the chemistry of aryldiazonium cations, with the objective of offering a scalable one-step route to the covalent immobilization of glycans onto surfaces ranging from metals, to carbon and polymers. In this work we will discuss the applications of passive saccharide layers for fouling mitigation in aqueous media. Results of laboratory and field tests show that aryldiazonium functionalization with glycans can be used to reduce biomass accumulation on polymeric and alloy structural components, as well as in electroactive components in biomass-rich media. Furthermore, we report on the use of this methodology for the creation of well-defined active saccharide layers for affinity capture and sensing.

Resume : The aim of the study was to obtain a polylactide spongy bone implant to be a carrier of platelet rich plasma (PRP). Polylactide (PLA) demonstrated osteoconductive properties in many clinical trials, however insufficient in the case of larger defects healing. PLA need to be provided together with bone growth factors included for example in PRP. Deposition of calcium phosphate salts was applied both to increase the absorbability of hydrophobic PLA with PRP and to facilitate the osteoinductive properties of the implant. PLA implants were obtained by the freeze-extraction method, then were modified through a biomimetic deposition of calcium phosphate salts. The efficiency of the mineralization process was increased. Implant surface was characterized by SEM, FTIR and EDS analysis. Mass absorbability and open porosity of implants were measured by the hydrostatic weighing method. Obtained implants were soaked with animal plasma through static soaking and centrifugation. The presence of plasma inside the implant was determined by EDS, FTIR and elementary analysis. Influence of centrifugation with plasma on the internal morphology was determined by SEM. Implants with open porosity above 80% and volume of about 10 cm3 were obtained. Mass absorbability with isopropanol was up to 1400%. Mineralization process enabled the plasma to enter the internal structure of PLA implant. Mass absorbability with plasma was in a range of 350-1700% depending on the soaking mode and mineralization type.

Resume : The neurodegenerative disorder Parkinson’s disease (PD) is caused by a degeneration of dopaminergic neurons, and linked genetically and neuropathologically with a presynaptic neuronal protein, alpha-synuclein (SNCA). Molecularly imprinted polymers (MIPs) can often bind target molecules with high selectivity and specificity. When used as MIPs, conductive polymers may provide better electrochemical performance than that by conventional MIPs. In this work, an electrochemical method was used to optimize the synthetic self-assembly of poly(hydroxymethyl 3,4-ethylenedioxythiophene) with one peptide of SNCA, forming peptide-imprinted electrically conductive polymers (PIPs) on sensing electrodes. The surfaces of poly(EDOT-OH) films exhibited homogeneous tubular microstructures from their scanning electron microscope (SEM) images. The linear sensing range for peptide/SCNA ranged from 10-7 to 100 fg/mL, and the limit of detection was as low as ~aM. The culture medium from the differentiation of midbrain organoids in microfluidics chips was collected and measured. However, the measured SCNA concentrations in the culture medium are less than ~ag/mL, which is much small than that in cerebrospinal fluid (CSF, ~ng/mL). (This work was supported by MOST 106-2221-E-390-013-MY3 and MOST 107-2923-M-390-001-MY3 from the Ministry of Science and Technology of ROC, Taiwan.) References: 1. Mei-Hwa Lee, James L. Thomas, Yu-Chia Chang, Yuh-Shyan Tsai, Bin-Da Liu and Hung-Yin Lin*,” Electrochemical Sensing of Nuclear Matrix Protein 22 in Urine with Molecularly Imprinted Poly(ethylene-co-vinyl alcohol) Coated Zinc Oxide Nanorod Arrays for Clinical Studies of Bladder Cancer Diagnosis,” Biosensors and Bioelectronics, 79, 789-795, 2016. 2. Mei-Hwa Lee, Danny O’Hare, Han-Zhang Guo, Chien-Hsin Yang* and Hung-Yin Lin*,” Electrochemical Sensing of Urinary Progesterone with Molecularly Imprinted Poly(aniline-co-metanilic acid)s,” Journal of Materials Chemistry B, 4, 3782-3787, 2016.. 3. Shyh-Chyang Luo, James L. Thomas, Han-Zhang Guo, Wei-Tang Liao, Mei-Hwa Lee and Hung-Yin Lin*,” Electrosynthesis of Nanostructured, Imprinted Poly(hydroxymethyl 3,4-ethylenedioxythiophene) for the Ultrasensitive Electrochemical Detection of Urinary Progesterone,” ChemistrySelect, 2, 26, 7935-7939, 2017. 4. Mei-Hwa Lee, James L. Thomas, Chun-Lin Liao, Stipo Jurcevic, Tatjana Crnogorac-Jurcevic and Hung-Yin Lin*,” Epitope Recognition of Peptide-imprinted Polymers for Regenerating Protein 1 (REG1),” Separation and Purification Technology, 192, 213-219, 2018.

Resume : Multilayer graphene (MLG) on Insulators will lead to various advanced electronic devices. Graphene has a unique two-dimensional structure, whose characteristics are anisotropic. In line with this, large-grained, highly oriented MLG on insulators has been widely investigated. The layer exchange technique enables high-quality multilayer graphene (MLG) on arbitrary substrates, which is a key to combining advanced electronic devices with carbon materials.[1-3] In this study we synthesize uniform MLG layers of various thicknesses, t, ranging from 5 nm to 200 nm using Ni-induced layer exchange at 800 °C. Raman and transmission electron microscopy studies show the crystal quality of MLG is relatively low for t ≤ 20 nm and dramatically improves for t ≥ 50 nm when we prepare a diffusion controlling Al2O3 interlayer between the C and Ni layers. Hall effect measurements reveal the carrier mobility for t = 50 nm is 550 cm2/Vs, which is the highest Hall mobility in MLG directly formed on an insulator. The electrical conductivity (2700 S/cm) also exceeds a highly oriented pyrolytic graphite synthesized at 3000 °C or higher. Synthesis technology of MLG with a wide range of thicknesses will enable exploration of extensive device applications of carbon materials. [1] Murata et al., APL. 110, 033108 (2017). [2] Murata et al., APL. 111, 243104 (2017). (Highlighted in Nature INDEX.) [3] Y. Nakajima, H. Murata et al., ACS AMI. 10, 41664 (2018).

Resume : Multimodal agents are gaining a worldwide spread interest due to their diagnostic and therapeutic (theranostic) feasibility in cancer treatment. Photothermal therapy (PTT) is the latest, localized approach to cancer therapy. It utilizes nanoparticles which can transform absorbed light, usually in the infrared (IR) region, into the heat inside a living cell leading to cell death. Here we present synthesis and characterization of new hybrid bioinspired nanomaterials based on polydopamine and fluorescent nanodiamonds capable of simultaneous PTT and imaging. In our approach first, we developed a method to control the size of the polydopamine particles in a range from 40 to 200 nm. As obtained nanoparticles were modified to introduce carboxylic groups that further are used to attach well-dispersed fluorescent nanodiamonds (fNDs). This method allows avoiding the fluorescence quenching by PDA , provide excellent biocompatibility and high photothermal response. Additionally, the introduction of metal ions into such a system is discussed. In summary, an effective protocol for a preparation multifunctional nanoparticles for combined PTT and imaging technique, comprised of known biocompatible components is introduced with high potential application in nanomedicine.

Resume : Poly(3,4-ethylenedioxythiophene) (PEDOT) materials was widely used in fabricating bioelectronic devices 1-4 as it possessed excellent electrical conductivity and electrochemical stability5,6. Fabricating functionalized PEDOT materials with proper nanomorphologies via template-free methods would significantly enhance the potential applications in the field of bioelectronics. To simplify the fabrication process and used in large scale, template-free assembling was necessary. In this work, we fabricated various functionalized PEDOT thin films with nanodot nanotube morphologies via template-free electrochemical depositing. Little amount of water was added into the electrochemical solution and led to the transforming of surface structure from nanodot to nanotube. Phase separation was thought to be the main reason for the assembling of nanotube surface structure. The diameter, length and density of nanotubes could also be tuned. Glancing incident wide angle XRD was measured and found that the nanodot and nanotube thin film possessed differenct crystal orientations, which could be used to propose the possible formation process of nanodot and nanotube morphologies. Besides, we had proved that the nanotube functionalized PEDOT thin films possessed enhanced electric and biological properties compared with flat and nanodot thin films using in bioelectrode arrays. Reference: 1. Khodagholy, D.; Rivnay, J.; Sessolo, M.; Gurfinkel, M.; Leleux, P.; Jimison, L. H.; Stavrinidou, E.; Herve, T.; Sanaur, S.; Owens, R. M.; Malliaras, G. G. Nat Commun 2013, 4, 2133. 2. Rivnay, J.; Inal, S.; Collins, B. A.; Sessolo, M.; Stavrinidou, E.; Strakosas, X.; Tassone, C.; Delongchamp, D. M.; Malliaras, G. G. Nat. Commun. 2016, 7, 11287.

Resume : Nanodispersed titanium dioxide is successfully used to convert and accumulate solar energy, eliminate toxic contaminants, technology for obtaining valuable chemical compounds, as well as to obtain composite materials that possess antibacterial properties. Such materials can be used to create antibacterial ceramics, bactericidal medical equipment, surgical instruments, packaging for food products, etc. The photocatalytic and antibacterial properties of nanodispersed TiO2 obtained by high-temperature hydrolysis of titanium tetrachloride vapors in air-hydrogen flame at a temperature of 700-1100 ºС are investigated in the work by methods of computer analysis and intelligent data processing. It was shown that samples of nanodispersed titanium dioxide have a non-stoichiometric structure containing crystalline modifications of anatase and rutile and have high photocatalytic activity in the methylene blue recovery and oxidation reaction of iodide ions and antibacterial activity in relation to pathogenic Staphylococcus aureus and Escherichia coli microorganisms. It has been established that the antibacterial effect of the suspension containing 1.0 wt. % nanodispersed titanium dioxide is commensurate with the action of the antibiotic novobiocin. Antibacterial activity of suspensions containing 5.0 and 10.0 wt. % TiO2 in relation to gram-negative microorganisms Escherichia coli significantly exceeds the bactericidal effect of novobiocin. The effectiveness acting of nanodispersed TiO2 on gram-positive microorganisms of Staphylococcus aureus is less than on the gram-negative microorganisms of Escherichia coli.

Resume : Undoped and doped biological-derived hydroxyapatite (HA) coatings (of animal origin) were synthesized by Pulsed Laser Deposition onto medical grade titanium substrates. The role of doping reagents on the morphological, structural, bonding strength and cytocompatibility of structures was investigated. Morphological examination evidenced the fabrication of rough surfaces, ideal for the good adhesion of cells and anchorage of implants in situ. Structural investigations demonstrated that the synthesized structures consisted of a pure HA phase, with different degrees of crystallinity mainly influenced by the reinforcing agents. Compositional analyses revealed the presence of typical natural doping elements of bone, along with a quasi-stoichiometric target-to-substrate transfer. In the case of undoped structures, a hydrophilic behavior was evidenced, which is known in the literature to be related to an improved surface attachment of osteoblast cells. The inferred bonding strength values were superior to the threshold imposed by ISO standards regulating load-bearing implant coatings. After only three days of immersion in simulated body fluids, a remarkable growth of a biomimetic apatitic layer was observed. This was indicative of a high biomineralization capacity of coatings. Moreover, the synthesized layers exhibited an excellent biocompatibility, corroborated with a long-lasting anti-staphylococcal and ?fungal biofilm activity. Along with low fabrication costs, these combined characteristics could offer guidance towards the suitability of using these bioinspired HA materials for the fabrication of a new generation of implant coatings. Acknowledgements: This work was supported by a grant of Ministry of Research and Innovation, CNCS-UEFISCDI, No. PN-III-P1-1.1-PD-2016-1568 (PD 6/2018), within PNCDI III. LD and VC acknowledge also the support of the Core Programme 16N/2019.

Resume : As spider silks have extraordinary mechanical properties, the design of high performance artificial silk fibers has been one of the focuses in the field of biomimetic fibers. Cellulose nanofibers (CNF) have considerable potential being an effective reinforcing agent in biocompatible composites for their high aspect ratio, good stiffness of the crystalline regions and biocompatibility. In this study, regenerated silk fibroin (RSF) / CNF hybrid fibers were dry-spun through a microfluidic chip, which mimicked the shape of spider’s major ampullate gland. The results showed that the presence of CNF could substantially enhance the mechanical properties of RSF. In specific, the break strength of the RSF/CNF fibers with 1 wt‰ CNF was increased to 486 ± 106 MPa with a maximum value of 686 MPa, significantly higher than that of silk fibers from silkworm. The enhancement could be attributed to higher orientation of crystalline and mesophase contents, higher crystallinity and hydrogen bonds linked between RSF and CNF. The study outlined a new pathway to generate artificial silks with high performance properties.

Resume : The highest conversion efficiency of solar cells has been updated with III–V compound semiconductors. However, these solar cells use expensive single-crystal Ge or GaAs-based wafers. Therefore, research to synthesize a high-quality GaAs film on an inexpensive substrate has been continuing for decades in the quest to develop a solar cell that achieves both high-efficiency and low-cost. In particular, GaAs solar cells fabricated on flexible plastic substrates will open up the possibility for developing advanced wearable devices. Therefore, we have recently been studying low temperature synthesis of high-quality GaAs films on insulators. In this study, we applied a large-grained Ge layer on a glass substrate, formed by Al-induced layer exchange (ALILE) [1], to a molecular beam epitaxy template for a GaAs film. The GaAs film grown at 520 °C exhibited large grains (> 100 μm) with high (111) orientation, indicating epitaxial growth from the ALILE-Ge seed layer, while the GaAs film directly grown on glass has very small grains (< 100 nm). The photoresponsivity measurement showed that the internal quantum efficiency reached 70% under a bias voltage of 1.0 V [2]. This value approaches that of a simultaneously formed GaAs film on a single-crystal Ge wafer and is the highest for a GaAs film synthesized on glass at a low temperature. Thus, the pseudo-single-crystal GaAs layer (grain size > 100 μm) was achieved below the heat-proof temperature of general soda-lime glass. Further lowering the growth temperature (< 500 °C) will lead to novel flexible GaAs solar cells based on plastic substrates. [1] K. Toko et al., APL. 104, 022106 (2014). [2] T. Nishida et al., APL. 114, 142103 (2019).

Resume : Although considerable research has been conducted on the use of 2D materials as drug delivery systems, very little is still known about the subsequent fate of the carrier. The design of smart multifunctional materials able to both selectively deliver a drug into cells in a targeted manner and display an enhanced propensity for biodegradation is crucial. Here, graphene oxide (GO) is functionalized with the chemotactic peptide N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) known to interact with the formyl peptide receptor, which is expressed in different cancer cells, including cervical carcinoma cells. This study highlights the ability of GOfMLP for targeted drug delivery and cancer cell killing and the subsequent degradation capacity of the hybrid. We demonstrate that GOfMLP is susceptible to a faster myeloperoxidase mediated degradation. The hybrid material, but not GO, is capable of inducing neutrophil degranulation with subsequent degradation, being the first study showing inducible neutrophil degradation by the nanomaterial itself with no prior activation of the cells. Moreover, confocal imaging and flow cytometry using HeLa cells show that GOfMLP is able to deliver the chemotherapeutic agent doxorubicin faster into cells, inducing higher levels of apoptosis, when compared to non-functionalized GO. Overall, this work reveals that GOfMLP is a promising carrier able to efficiently deliver anti-cancer drugs, being endowed with the capacity to induce its own biodegradation.

Resume : We present an overview of our studies on the synthesis and investigation of water-soluble fullerene derivatives (WSFs). Chlorofullerenes C60Cl6 and C70Cl8 were shown to be ideal precursors for synthesis of various WSFs. Friedel-Crafts type reactions led to big families of C60 and C70 derivatives bearing appended fragments of arylalkylcarboxylic and aryloxyalkylcarboxylic acids [Org. Biomol. Chem., 2019, 10.1039/C9OB00593E, Chem. Commun., 2011, 47, 8298]. Novel reactions with amines, amino acids [Chem. Commun., 2012, 48, 5461], thiols, thioacids [Chem. Commun., 2012, 48, 7158; Tetrahedron Lett. 2016, 57, 1215], trialkylphosphites [Chem. Commun., 2012, 48, 8916; Tetrahedron Lett. 2016, 57, 5570], and alcohols [Org. Biomol. Chem., 2017, 15, 773; Tetrahedron Lett., 2017, 59, 605] produced new classes of WSFs. Toxicity and different types of biological activity of the prepared WSFs will be discussed. A particular attention will be paid to antiviral activity. It is commonly believed that anti-HIV action of WSFs is related to the HIV protease inhibition. We will prove with many examples that this belief is not correct in many cases and WSFs actually inhibit multiple other HIV targets. Moreover, examples of WSFs demonstrating impressive activity against influenza, herpes simplex virus, cytomegalovirus, etc. confirm great potential of using water-soluble nanocarbon materials in biomedicine and drug design.

Resume : Polydiacetylenes are mechanochromic polymers, that show a change (e.g. chromism, fluorescence, electrical properties (1) etc.) upon external stimuli such as heat, stress or changes in chemical environment (2, 3). However, how these stimuli influence their structure (4) and how that relates to their optical properties is still not clear to this day. To address these questions, we deposited 10,12-tricosadiynoic acid onto plasma-activated glass substrates, exposed to UV for polymerisation, and applied forces to the polymerised film by an atomic force microscope, while simultaneously measuring the emitted fluorescence. The fluorescence is characteristic of the transformed red phase of polydiacetylenes, thus enabling us to follow the phase transition, while the atomic force microscope registers the forces exerted to the polydiacetylene chains. Combining the two techniques could open a path to the fluorescence – force calibration of the colour change, contributing to a deeper understanding of polydiacetylenes. 1. Girard-Reydet C, Ortuso RD, Tsemperouli M, Sugihara K. Combined Electrical and Optical Characterization of Polydiacetylene. J Phys Chem B. 2016;120(14):3511-5. 2. Wen JT, Roper JM, Tsutsui H. Polydiacetylene Supramolecules: Synthesis, Characterization, and Emerging Applications. Ind Eng Chem Res. 2018;57(28):9037-53. 3. Ortuso RD, Cataldi U, Sugihara K. Mechanosensitivity of polydiacetylene with a phosphocholine headgroup. Soft Matter. 2017;13(8):1728-36. 4. Ortuso RD, Ricardi N, Burgi T, Wesolowski TA, Sugihara K. The deconvolution analysis of ATR-FTIR spectra of diacetylene during UV exposure. Spectrochim Acta A Mol Biomol Spectrosc. 2019;219:23-32.

Resume : Cellulose nanofibrils are biodegradable, renewable, intrinsically amphiphilic and possess outstanding mechanical properties, thanks to their high weight-to-strength ratio, obtained through cellulose pulp disintegration. Nanocellulose foams are attracting an increasing attention for their potential in a wide variety of applications, where low density and high surface areas are required, including filtration processes, gas adsorption and selective liquid absorption for remediation of polluted areas. One commonly used technique to fabricate nanocellulose foams is based on ice templating, through the well-known freeze-drying process, in which an aqueous suspension of cellulose nanofibrils is frozen by liquid nitrogen and vacuum-dried, to obtain dry foams. However, vacuum drying is a high energy-consuming step, and currently represents a bottleneck for the process scale-up, needed for industrially relevant applications. As such, the current study approaches the issue of how to improve the ice template strategy, avoiding the vacuum-drying step, while achieving extremely high porosity. To address the issue, we present a novel straightforward freeze-thawing-drying procedure, taking advantage of urea as additive to the aqueous cellulose nanofibril suspension and of solvent exchange. Such method allows the production of mechanically stable, lightweight cellulose-based structures, avoiding foam collapse, upon facile thawing-drying steps. Functionalization of porous foams imparts a hydrophobic-oleophilic wetting property, which can be used for selective oil absorption, as demonstrated by impact tests with multiphase water-in-oil compound drops.

Resume : Carbon nanotube (CNT) films have satisfactory optical and electrical parameters, as well high mechanical and thermal stability. The addition of a conductive polymer to a CNT film can significantly reduce the contact resistance between individual CNT’s and increase the transparency - surface resistance ratio. The possibility of layer-by-layer formation of composite films with enhanced conductivity based on the system of CNT’s - conducting polymer using the in-print method demonstrated. The main advantage of the films obtained is the mechanical stability to bending deformations. The impedance characteristics of samples based on modified CNT films studied. A numerical method proposed, which makes it possible to approximate the distribution functions of the relaxation times of active R, reactive C and L elements of samples directly from the experimentally obtained frequency dependence of the real and imaginary components of the impedance. The films characterized by a combination of low surface resistance (156 ohms/sq.) and low optical transparency (~ 32 %). It shown, increasing contains of CNT’s in film, the conductivity of the samples height.

Resume : Silicon quantum dots (SiQDs) are highly photoluminescent semiconductor nanoparticles that continue to attract interest as promising materials for medical diagnostics and chemical/biological sensing. Their biocompatibility and nontoxicity make them an attractive alternative to the more popular but cytotoxic cadmium-based quantum dots for biological applications. Elastin-like polypeptides (ELPs) are biological polymers that have chemical structures based upon the mammalian protein elastin. They undergo reversible phase transition and assemble into nanoscale and microscale structures in response to changes in temperature, pH, and ionic strength, among others. We report herein the preparation of hybrid materials from SiQDs and ELPs through the amide coupling reaction. Successful conjugation of ELPs to the SiQDs was confirmed through Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The hybrids retain the characteristic intense orange photoluminescence and microsecond excited state lifetimes of the SiQDs and the thermal responsiveness of the ELPs. They form photoluminescent microscale assemblies upon heating, which then dissociate back into individual nanoparticles upon cooling, as confirmed by dynamic light scattering analysis. The hybrids prepared herein offer an attractive platform in biomedical and sensing applications where spatio-temporal control over probe behavior is of paramount importance.

Resume : Currently, biocybernic systems are used in medicine, in particular for the restoration of patients after severe traumas of the locomotorium, in biotechnology and ecology for monitoring the state and forecasting of the development of ecosystems, in pharmacy and scientific research to measure and analyze the spectrometric characteristics of bioobjects, etc. The main problem that arises in this is the large amount of data arrays that often require processing and analysis in real time. The purpose of these studies is to develop methods for increasing the accuracy of on-line telemetry of bioobjects and reducing the time of their analysis. In the given work the method of complex monitoring and express analysis of the state of the investigated ecosystem is offered. Its essence is to find the problem areas of the investigated characteristics of the bioobject, and to find the deviations of the controlled parameters from the admissible limits in the identified areas with a more detailed study at the next stage. Criteria for finding problem areas are the results of computer real-time data processing on a remote server. This allows you to optimize hardware and software and minimize the resources of the mobile telemetry complex. Thanks to the use of Internet technology, such a complex can be realized on the basis of a smartphone. To this end, special protocols for network data protection have been developed. Experimental testing of the proposed method in the spectral studies of carcinogenic components in bioactive media and materials shows that the time of rapid analysis of bioobjects is reduced by 3-5 times, and the accuracy of detection of characteristic spectral lines increases by 10-15%.

Resume : Nanowires have been attracting great interest for numerous applications. In particular, their dimensions that are comparable to those of biomolecules, as well as their ultra-high aspect ratio and mechanical flexibility, make them very attractive for mimicking physiological environment of cells in the fundamental studies of the cell-environment intentions. To provide nanowires with the ability of chemical signaling they are often functionalized with signaling molecules. However, such a functionalization, based on either chemisorption or physisorption of biomolecules has not been site specific. Here, we took advantage of the fact that chemical-vapor-deposition grown nanowires carry on their tips metallic catalytic nanoparticles, to achieve the first of its type site selective functionalization of biomolecules. Such functionalization comes to provide a biomimetic 3D cell environment with precisely positioned biomolecules. We have grown Si nanowires from Au catalyst. We covered Au tips with biotinylated thiols, and used Neutravidin bridge to attach to the molecules of biotinylated anti-NKp30 – an activating ligands for Natural Killer cells, which are lymphocytes of the innate immune system. To study the effect of clustering at both nanometric and micron scale on cells, we investigated the effect of continues bed of nanowires verses micropatterned areas of nanowires. Further, we varied the stiffness of nanowires by changing their length and followed its effect on cell population.

Resume : The actual trend in developing sensor technologies, especially for wearable and skin devices, pushes toward biocompatible materials, allowing future applications to became sustainable, economic and environment friendly. Chitosan aims at becoming a key material for future electronics due its unique properties: biocompatibility, biodegradability, hydrophilicity, non-toxicity. In this study, the surface of SnO2 nanowires was functionalized by the chitosan layer for room-temperature conductometric humidity sensing. SnO2 nanowires have been synthesized by seed-mediated CVD method. The chitosan powders 0.3 gr (CAS no: 1912-76-4) was dissolved in acetic acid aqueous solution (1.5%) and afterwards deposited on top of SnO2 nanowires by spin coating method. The surface morphologies, crystal structures and optical properties of the synthesized hybrid nanostructures were investigated by scanning electron microscope, grazing incidence X-ray diffraction and UV-vis absorption measurements. During electrical conduction measurements, the hybrid nanostructures showed different sensing response towards various relative humidity (RH) concentrations (25%, 50%, 75%), under UV-light irradiation and dark conditions. The highest sensor responses have been recorded towards RH of 75%, resulting in 1.1 under dark and 2.5 under UV irradiation. A change in conduction mechanism and different recovery trends has been observed in chitosan@SnO2 measurements under UV light irradiation and dark conditions.

Resume : Implant surgery is often accompanied by a bacterial infection related to biofilm formation on their surfaces. Already grown biofilm is very difficult to treat because such bacteria are more resistant against most of the antibiotics. An alternative way is to cover the implant by the smart antibacterial film. Besides the antibiotics, the antibacterial metals can be used as an antibacterial agent. The nanocomposites consisted of Cu nanoparticles fixed in water-permeable plasma polymer matrix acting as a diffusion barrier can offer a large metallic surface for ion production, while maintaining the negligible amount of metal in the patient body. The sandwich nanostructures were fabricated by the sequential deposition of plasma polymer and nanoparticles prepared by means of gas aggregation nanoparticle source. The vacuum-based beam deposition of nanoparticles allowed (i) their high purity grade fabrication and (ii) their homogeneous deposition over a large area. The huge advantage of nitrogen-rich plasma polymers is their ability to immobilize antibiotics (ampicillin and ciprofloxacin). Antibiotics loading is strongly connected to film chemical composition, meanwhile, their release can be controlled by an additional diffusion barrier. The problem of bacteria getting resistant by long-term antibiotics dosing can be elegantly solved by multistage antibacterial action of quicky released antibiotics accompanied with long-term metallic ion release. Supported by GACR 19-20168S

Resume : The intense development of amorphous transparent conducting oxide (a-TCO) materials spurred by a great interest in the production of 4K displays and flexible electronics. Nowadays a-InGaZnO is one of the dominant materials in the field of thin film transistors (TFTs) for displays production. However, it has significant drawbacks such as toxicity that causes fibrosis when inhaled [1], shortage of supply and high cost. Therefore there is a demand for finding an environmentally and cost friendly alternative. An Indium free amorphous transparent conducting oxide made of nontoxic abundant elements that have the potential to occupy that niche is a-ZnSnO. It has high conductivities along with innate resistance to degradation upon bending and relatively low deposition temperatures. Moreover, recently some reports suggesting the developments of oxide TFT sensors for detecting DNA, enzyme, and organic solvents emerged [2]. Therefore, small-sized and high-density TFT arrays have can be effectively utilised in as portable sensors at low cost with positive implications for the direct and rapid medical diagnosis [3]. The broad range of application of a-ZnSnO requires a detailed compositional study of the material because the performance of the constructed device will be dramatically influenced by the properties. On that account this work focused on extensive Zn/Sn composition analysis of co-sputtering grown a-ZnSnO. By utilizing Hall measurements, X-Ray Diffraction/Reflection (XRD/XRR), X-ray Photoelectron Spectroscopy (XPS) and post deposition heat treatment we were able to link electrical properties (mobility, conductivity and carrier concentration) of a-ZnSnO to its composition. This analysis brings into a view a fact that the relationship between the Zn/Sn ratio and the electrical properties of the material can vary depending on the deposition technique employed and imply that for particular applications certain deposition techniques are preferable. 1. Bomhard E., Environmental Toxicology and Pharmacology, 2018, 58 2. Jiang Q., at al, RSC Adv., 2015, 5, 28242 3. Kim S., at al, ACS Appl. Mater. Interfaces 2013, 5, 21, 10715-10720

Resume : In 2012, we published our groundbreaking study on mechanically responsive nanometer-size liposomes [1]. These liposomal nano-containers, composed out of specific artificial phospholipids, exhibit not only the desired response to mechanical stimuli [1], but also the surprising lack of the characteristic immune response of liposomal drugs [2-4]. As a consequence, these non-spherical liposomes are promising containers for the targeted release of vasodilators by a purely physical trigger present at the pathological constrictions of human atherosclerotic vessels. Very recently, we discovered, which forces modify the liposome?s structure and could be responsible for the release of the cargo. Originally, we have only considered the shear stress that is at least an order of magnitude higher within the constrictions than in the healthy parts of the vessel. Now, we are convinced that the pressure-gradient forces could also play an important role. The impact of these contributions is experimentally addressed by combining spatially resolved small-angle X-ray scattering with a microfluidic device for physically simulating the stenosed blood vessel [5]. [1] M. N. Holme et al.: Shear-stress sensitive lenticular vesicles for targeted drug delivery, Nature Nanotechnol 7 (2012) 536 [2] S. Bugna et al.: Surprising lack of liposome-induced complement activation by artificial 1,3-diamidophospholipids in vitro, Nanomed NBM 12 (2016) 845 [3] M. Buscema et al.: Immunological response to nitroglycerin-loaded shear-responsive liposomes in vitro and in vivo, J Control Release 264 (2017) 14 [4] S. Matviykiv et al.: Immunocompatibility of Rad-PC-Rad liposomes in vitro, based on human complement activation and cytokine release, Precision Nanomed 1 (2018) 45 [5] M. Buscema et al.: Spatially resolved small-angle X-ray scattering for characterizing mechanoresponsive liposomes using microfluidics, Materials Today Bio 1 (2019) 100003

Resume : Various design and functionalization strategies are used nowadays for obtaining multifunctional coatings based on biodegradable and biocompatible materials for targeting cells activity and enhancing cellular the bio-response. Specific examples include active compounds including from carbon based materials, to ceramics or to proteins are used for enhancing cellular response. In the last years, recent studies showed that the distribution of ceramic nanoparticles for instance and other bioactive compounds presence havecould influence significantly influence for nano-composites interfaces for osteoblasts responses envisaging osseous implant application. Herein we propose focused on embedding hydroxyapatite (HA) spherical nanoparticles and lactoferrin (LF) within synthetic biodegradable copolymers of Poly(ethylene glycol)-block-poly(ε-caprolactone) methyl ether (PEG-block-PCL Me) for the preparation ofto create new nanocomposites coatings capable of targeting and the modulating theed response of 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 through using a modular target system. The resulting morphologies and the main features characteristics of the “doped” samples were investigated using Atomic Force Microscopy (AFM) and Scanning Electron Microscopy (SEM). Fourier Transform Infrared Spectroscopy (FTIR) was also used with results showing that 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. Lastly, the behaviour of the coatings during immersion experiments were evaluated and correlated to their bio-functionality of the coatingsto derive structure-function relationships that enhanced cellular responses. 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. Further, and that model cells ofthe MC3T3-E1 murine osteoblasts responses in vitro (cell adhesion/morphology, proliferation and matrix mineralization) was differentially influenced by the variations in the physicochemical characteristics of materials biointerface demonstrating user-controlled ability (as dictated by MAPLE) to enhance bio-responses at living-non-living interfaces.

Resume : Deregulated expressions of surface receptors are promising biomarkers of many human diseases, notably cancer. However, targeting these biomarkers is often challenging due to a lack of receptor molecules. Molecularly imprinted polymers (MIPs) are tailor-made synthetic receptors (antibody mimics), able to specifically recognize target molecules. They are synthesized by co-polymerizing functional and cross-linking monomers in the presence of a molecular template, resulting in the formation of binding sites with affinities and specificities comparable to those of natural antibodies. Herein, we demonstrate the biotargeting of a cancer protein biomarker with MIP nanoparticles. MIPs were synthesized using a solid-phase synthesis approach in which a terminal peptide of the protein, selected as epitope, was immobilized on glass beads (as solid support) via click chemistry. This configuration allows an oriented immobilization of the template upon which thermoresponsive MIP nanoparticles are synthesized. The binding sites of the resulting MIPs all have the same orientation, thus MIPs synthesized by the solid-phase approach can be considered analogous to monoclonal antibodies. MIPs (50 nm) were found to bind the peptide epitope with high (nanomolar) affinity and selectivity as demonstrated by equilibrium binding assays with the peptide fluorescently labelled. Mutation of a single amino acid in the peptide sequence resulted in a reduced affinity by three orders of magnitude. Rhodamine-doped MIPs were used for fluorescence imaging to reveal the recognition of the target protein on epithelial cells. When the protein biomarker was hydrolytically removed from the cells, staining was dramatically decreased. In addition, very similar staining patterns were obtained at immunostaining with monoclonal antibodies. The ability of MIPs to modulate the function of the surface receptor was further demonstrated on live cells. The application of MIPs as therapeutic agents is being studied.

Resume : Polyelectrolytes have many applications from water treatment, food industry to bio- and medical applications. In the last years, their use to surface modification as multilayers systems is subject of research. Our studies have focused on combination polyethyleneimine – alginate polyelectrolytes. We prepared a series of multilayered systems to observe the influence of time order of deposition on the obtained films morphology (AFM), thickness (lithography method) and chemical structure (XPS). The chosen pair of electrolytes efficiently form a well-mixed (interdiffusion) layers. The obtained multilayered systems show the sorption properties towards ferricyanide ions. We decided to use this property with respect to other ions, using films obtained by flocculation method. The sorption capacity up to 350 and 550 mg/g for Cu and Cd ions respectively was observed.

Resume : In this lecture, we will discuss the applications of real-time intravital imaging in various disease models. We are interested in the real-time imaging of the circulating tumor cells (CTCs). CTCs are very important for tumor metastasis. The number of CTCs has been used as an indicator for the progress of a tumor state. However, the way in which CTCs travel in the bloodstream and the way in which they cross the endothelial barrier are not known. We will discuss the way in which to utilize the real-time intravital imaging system to monitor the behavior of individual CTCs and the subpopulation of CTCs. CTCs can travel from primary tumors through the circulation to form secondary tumor colonies via bloodstream extravasation. 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.

Resume : Tightening environmental regulations and increasing awareness for the need to protect the ecosystem have effectively resulted in an increasing interest in biosurfactants as possible alternatives to chemical surfactants. They have advantages over their chemical counterparts in specificity, relative ease of preparation, mildness, nontoxicity, excellent biodegradability, possibility of large-scale production, selectivity, and effectiveness even at extreme temperature or pH. In this study, 3 types of zwitterionic phospholipid biosurfactants were prepared using 3 different raw materials such as rapeseed oil , coconut oil, and cottonseed oil respectively and the structure of the resulting products was elucidated by FT-IR, 1H NMR, and 13C NMR spectroscopies. Biodegradability, acute oral toxicity (LD50), acute dermal irritation and acute eye irritation tests revealed that the newly synthesized biosurfactants possess excellent mildness and superior environmental compatibility as well as superior interfacial properties, indicating the potential applicability in cosmetic product formulations. The patch test result has shown that the newly prepared biosurfactants indicated no allergic inflammation on a skin during 48 hrs. The prescription test in shampoo formulation prepared with the newly synthesized biosurfactants indicated excellent sensory feeling and foam ability compared with conventional hydrocarbon and silicon surfactants. ACKNOWLEDEMENTS This work was supported by "the Global Tech Company Nurturing Program“(N063600016, Development of eco-friendly multifunctional polymer surfactant with preservative function and next generation polymer surfactant for construction) funded by the Ministry of Trade, Industry & Energy, Korea.

Resume : Biological synthesis of zinc chromate mixed oxide nanoparticulate using natural leaf extracts of Hibiscus Rosa Sinensis. This is a simple, cost-effective and reproducible aqueous room temperature synthesis method to obtain spinel cubic phase ZnCr2O4 mixed oxide nanoparticles. X-ray diffraction (XRD) confirmed nanoparticles were crystalline with particle size estimated 14 nm for ZnCr2O4nanoparticles annealed at 700 oC, 26 nm at 500 oC, 56 nm at 200 oC and 70 nm at room temperature (RT). High resolution- transmission electron microscope (HR-TEM) and HR-scanning electron microscope (SEM) confirmed particles size of nanoparticles are around (fparticles) 14.5 ± 2 nm for HRTEM and 60-70 nm sized agglomerated cubic shaped particles for HRSEM. Fourier transform infrared spectrum (FTIR) was used for structural analysis. The band gaps calculated from UV-vis diffused reflectance (DR) are for ZnCr2O4mixed oxide nanoparticles at RT and annealed at 200 oC, 500 oC and 700 oC are 2.47 eV, 2.40 eV, 3.19 eV and 3.09 eV respectively. fluorescence excitation was used to confirm band gaps of DR showing ZnCr2O4mixed oxide nanoparticles possess excellent photocatalytic activity.

Resume : We suggest a cell-in-shell (or artificial spore) strategy to enhance the cell viability in the practical settings, while maintaining biological activities for therapeutic efficacy. A durable titanium oxide (TiO2) shell is formed on individual Jurkat T cells by layer-by-layer deposition of TiO2-inducing peptides and TiO2 precursor. Resulting shell protect Jurkat T cells against external heat stress. Encapsulated cells are able to stay in a state of starvation for 2 weeks, and have a resistance against high temperature. On the other hand, because of the porosity of TiO2 shell, CD3 and other antigens on cell surfaces remain accessible to the antibodies. Jurkat T cells can be stimulated with molecules or model cells (antibody-presenting microbeads) and interleukin-2 (IL-2) secretion is also not hampered by the shell formation. This work suggests a chemical toolbox for effectively preserving lymphocytes in vitro and developing the lymphocyte-based cancer immunotherapy.

Resume : Ionic liquids are tailorable solvents with many potential applications, such as in electrochemistry, organic reactions, amphiphile self-assembly and protein stability. The field is trending towards using ionic liquids combined with a molecular solvent to decrease costs and improve properties, such as lowering viscosity. However, there is little knowledge about the fundamental properties of these multi-component solvents. In this study we used high throughput approaches to prepare large libraries of ionic liquids, and their mixtures with co-solvents. These were characterised using physico-chemical and Synchrotron SAXS techniques. Machine learning approaches were employed to develop structure-property models from this data and obtain design rules for future fit-for-function ionic liquids-solvent systems.

Resume : Titanium (Ti) and its alloys are widely used by the biomedical industry for implants design due to their suitable properties, such as: low Young's modulus, good corrosion resistance, biocompatibility and osseointegration. Besides, alloying elements like molybdenum (Mo), zirconium (Zr) and tantalum (Ta), which are considered non-cytotoxic metals, have been used to develop new beta Ti alloys. Considering their application, both corrosion and tribocorrosion resistances are important aspects to be considered, since they may lead to the accelerated degradation of the implant and the release of wear particles and ions. In this work, three different heat treatment conditions were applied to Ti-15Zr-15Mo system in order to increase its microhardness value (as cast, 600ºC/6h and 900ºC/8h). Then, the corrosion and tribocorrosion behaviors were investigated using open circuit potential (OCP), potentiodynamic (PD), electrochemical impedance spectroscopy (EIS) techniques. All samples were physicochemically characterized before and after (wear width and volume) each test and the obtained results were compared to those obtained for the most consolidated Ti alloy (Ti-6Al-4V). Our findings indicate an improvement in the corrosion and tribocorrosion behaviors, wear width and wear volume for Ti-15Zr-15Mo samples whose heat treatments resulted in higher microhardness values. However, all Ti-15Zr-15Mo samples presented inferior results when compared to Ti-6Al-4V.

Resume : As spider silks have extraordinary mechanical properties, the design of high performance artificial silk fibers has been one of the focuses in the field of biomimetic fibers. Cellulose nanofibers (CNF) have considerable potential being an effective reinforcing agent in biocompatible composites for their high aspect ratio, good stiffness of the crystalline regions and biocompatibility. In this study, regenerated silk fibroin (RSF) / CNF hybrid fibers were dry-spun through a microfluidic chip, which mimicked the shape of spider’s major ampullate gland. The results showed that the presence of CNF could substantially enhance the mechanical properties of RSF. In specific, the break strength of the RSF/CNF fibers with 1 wt‰ CNF was increased to 486 ± 106 MPa with a maximum value of 686 MPa, significantly higher than that of silk fibers from silkworm. The enhancement could be attributed to higher orientation of crystalline and mesophase contents, higher crystallinity and hydrogen bonds linked between RSF and CNF. The study outlined a new pathway to generate artificial silks with high performance properties.

Resume : DNA nanotechnology is a bottom-up nanotechnology taking advantage of DNA as either a biologically or synthetically produced polymer with self-assembling properties. The DNA origami methodology [1] folds a single-stranded phage DNA (scaffold) via hundreds of synthesised oligo DNAs (staples). It offers the feasible assembly of arbitrarily addressable structures at a size of around a hundred nanometres. Using this method, a number of encapsulating structures have been produced to date including a nanoscale box with controllable lid [2], a clamshell shaped nanorobot able to expose cargo in response to target signal [3] and a nanovault aiming to cage an active enzyme [4]. However, the encapsulation capacity and cargo isolation efficiency of such structures are still limited. Here we report the design of a two component capsule-shaped DNA origami nanostructure with each component having a cavity of ca 20 x 20 x 10 nm. The design offers full accessibility to anchored cargos when the shell is open while the closed form contains a cavity of approximately 11 attolitres. We evaluated cargo accessibility and the loading capacity of the DNA origami capsule as well as its ability to protect cargo using split GFP system as proof of principle. 1. Rothemund, P. W. Folding DNA to create nanoscale shapes and patterns. Nature 440, 297-302, doi:10.1038/nature04586 (2006). 2. Andersen, E. S. et al. Self-assembly of a nanoscale DNA box with a controllable lid. Nature 459, 73-76, doi:10.1038/nature07971 (2009). 3. Douglas, S. M., Bachelet, I. & Church, G. M. A logic-gated nanorobot for targeted transport of molecular payloads. Science 335, 831-834, doi:10.1126/science.1214081 (2012). 4. Grossi, G., Dalgaard Ebbesen Jepsen, M., Kjems, J. & Andersen, E. S. Control of enzyme reactions by a reconfigurable DNA nanovault. Nat Commun 8, 992, doi:10.1038/s41467-017-01072-8 (2017).

Resume : Carbon nanotube (CNT) films have satisfactory optical and electrical parameters, as well high mechanical and thermal stability. The addition of a conductive polymer to a CNT film can significantly reduce the contact resistance between individual CNT’s and increase the transparency - surface resistance ratio. The possibility of layer-by-layer formation of composite films with enhanced conductivity based on the system of CNT’s - conducting polymer using the in-print method demonstrated. The main advantage of the films obtained is the mechanical stability to bending deformations. The impedance characteristics of samples based on modified CNT films studied. A numerical method proposed, which makes it possible to approximate the distribution functions of the relaxation times of active R, reactive C and L elements of samples directly from the experimentally obtained frequency dependence of the real and imaginary components of the impedance. The films characterized by a combination of low surface resistance (156 ohms/sq.) and low optical transparency (~ 32 %). It shown, increasing contains of CNT’s in film, the conductivity of the samples height.

Resume : Multijunction solar cells using Ge in the bottom cell have updated the highest conversion efficiency of solar cells. However, bulk Ge substrates are expensive, which has limited their application to special uses. One promising approach to reducing the fabrication cost is substituting the bulk Ge substrate with a Ge thin film on inexpensive substrates such as glass or plastics. Al-induced layer exchange (ALILE) allows for large-grained (> 100 μm), (111)-oriented, and highly p-doped Ge thin films at low growth temperature (~350 °C) [1]. In this study, we adopted the Ge layer (thickness: 50 nm) formed by ALILE as an epitaxial seed of a high-quality light absorbing Ge layer (> 500 nm). After examining molecular beam epitaxy (MBE) and solid-phase epitaxy (SPE) for both methods, Ge layers with a low Al concentration were epitaxially grown at 350 °C. Microwave photoconductivity decay revealed that the MBE-Ge layer exhibited a short minority carrier lifetime owing to the rough surface. Conversely, the SPE-Ge layer was relatively flat and exhibited along bulk minority carrier lifetime (5.6 μs), which is close to that of a single-crystal Ge. Therefore, the seed layer concept that combines SPE with Al induced layer exchange is a promising way for fabricating ideal bottom cells for high-efficiency multijunction solar cells based on inexpensive substrates. [1] K. Toko et al., APL. 104, 022106 (2014).

Resume : Protein cages, due to their specific structure and characteristics, can have multiple applications, such as delivery systems or nanoreactors. They are usually built from multiple copies of the same protein, which are held together by hydrophobic interactions or hydrogen bonds. Virus capsids are an examples of a natural protein cage. It is of interest to try to mimic these unique structures but control of cage assembly, morphology and symmetry is difficult. Work in the Heddle Laboratory has suggested that artificial protein cages can be assembled not by complex weak interactions but by simple gold “staples”. In detail, certain gold nanoparticles and gold(I) compounds can interact with a cysteine-containing mutant of TRAP (trp-RNA attenuation protein) to promote protein-protein bonds, which can result in production of highly stable artificial protein cage structures. Moreover, by manipulating the gold to TRAP molar ratio two sizes of protein cage can be prepared: large cage, 21-22 nm and small cage, 15-16 nm. The Cryo-EM structure of large cage has been solved, but the structure of small cage is still unknown. In this work we attempted to characterise the small cage and to build its speculative model. We now have a clearer view on the control of protein cage formation. This understanding along with mechanistic implications will be presented.

Resume : Nanodispersed titanium dioxide is successfully used to convert and accumulate solar energy, eliminate toxic contaminants, technology for obtaining valuable chemical compounds, as well as to obtain composite materials that possess antibacterial properties. Such materials can be used to create antibacterial ceramics, bactericidal medical equipment, surgical instruments, packaging for food products, etc. The photocatalytic and antibacterial properties of nanodispersed TiO2 obtained by high-temperature hydrolysis of titanium tetrachloride vapors in air-hydrogen flame at a temperature of 700-1100 ºС are investigated in the work by methods of computer analysis and intelligent data processing. It was shown that samples of nanodispersed titanium dioxide have a non-stoichiometric structure containing crystalline modifications of anatase and rutile and have high photocatalytic activity in the methylene blue recovery and oxidation reaction of iodide ions and antibacterial activity in relation to pathogenic Staphylococcus aureus and Escherichia coli microorganisms. It has been established that the antibacterial effect of the suspension containing 1.0 wt. % nanodispersed titanium dioxide is commensurate with the action of the antibiotic novobiocin. Antibacterial activity of suspensions containing 5.0 and 10.0 wt. % TiO2 in relation to gram-negative microorganisms Escherichia coli significantly exceeds the bactericidal effect of novobiocin. The effectiveness acting of nanodispersed TiO2 on gram-positive microorganisms of Staphylococcus aureus is less than on the gram-negative microorganisms of Escherichia coli.

Resume : Deregulated expressions of surface receptors are promising biomarkers of many human diseases, notably cancer. However, targeting these biomarkers is often challenging due to a lack of receptor molecules. Molecularly imprinted polymers (MIPs) are tailor-made synthetic receptors (antibody mimics), able to specifically recognize target molecules. They are synthesized by co-polymerizing functional and cross-linking monomers in the presence of a molecular template, resulting in the formation of binding sites with affinities and specificities comparable to those of natural antibodies. Herein, we demonstrate the biotargeting of a cancer protein biomarker with MIP nanoparticles. MIPs were synthesized using a solid-phase synthesis approach in which a terminal peptide of the protein, selected as epitope, was immobilized on glass beads (as solid support) via click chemistry. This configuration allows an oriented immobilization of the template upon which thermoresponsive MIP nanoparticles are synthesized. The binding sites of the resulting MIPs all have the same orientation, thus MIPs synthesized by the solid-phase approach can be considered analogous to monoclonal antibodies. MIPs (50 nm) were found to bind the peptide epitope with high (nanomolar) affinity and selectivity as demonstrated by equilibrium binding assays with the peptide fluorescently labelled. Mutation of a single amino acid in the peptide sequence resulted in a reduced affinity by three orders of magnitude. Rhodamine-doped MIPs were used for fluorescence imaging to reveal the recognition of the target protein on epithelial cells. When the protein biomarker was hydrolytically removed from the cells, staining was dramatically decreased. In addition, very similar staining patterns were obtained at immunostaining with monoclonal antibodies. The ability of MIPs to modulate the function of the surface receptor was further demonstrated on live cells. The application of MIPs as therapeutic agents is being studied.

Resume : Falcarinol, found in carrot, parsley, celery and medicinal plant ginseng, has been identified as an active ant-cancer, anti-microbial, anti-inflammatory compound. Although its diacetylene structure indicates its potential to polymerize into polydiacetylene, a well-known mechanosensitive polymer in chemistry, almost nothing is known about its polymer form. Does falcarinol polymerize at all? If yes, how does it change its physiological properties? To answer these questions, in this work, we studied their supramolecular assembly by Langmuir-Blodgett trough, and characterize their structures by infrared (IR), Raman, and UV-VIS spectroscopy. All the data indicate that falcarinol polymerizes into a short-chain polymer under UV exposure only if they are aligned properly. Currently we are investigating the physiological properties of these polymerized falcarinol with cell culture.

Resume : In the framework of the density functional theory, changes in the structure and properties of calcium hydroxyapatite with the inclusions of carbonate ions are investigated. Different variants of carbonate ion positions, orientations and concentrations are considered. The study of changes in the structure and properties of hydroxyapatite with inclusions of carbonate ions is necessary for understanding the nuances of its interaction with collagen, since it is known that their bond is van der Waals and occurs through carbonate and hydroxyl. It has been established that in the case of the B-type isomorphous substitution, a violation of the classical structural organization of the carbonate ion occurs. The presence of a cationic vacancy leads to a substantial displacement of one of the oxygen atoms of the carbonate ion, which is reflected in the electronic states curve as narrowing the band gap. Composite materials based on hydroxyapatite and biocompatible polymers are characterized by the presence of carbonate residues in them, which requires more detailed studies on the incorporation of carbonate ions into the structure of apatite that began decades ago.

Resume : Protein assembly and amyloid fibrils aggregation is a huge matter in many of human diseases, such as Alzheimer’s and Parkinson’s.[1] Various bio-inspired artificial super-hydrophobic substrates (SHSs) were fabricated on silicon wafer for protein amyloid fibrils formation, deposition and analysis. The patterning of the surface was obtained with a combination of optical lithography and deep reactive ion etching (DRIE) technique on 4-inch Si <100> wafers with 500-um and 50-um thickness and the functionalization of the surface with hydrophobic material was achieved by the deposition of perfluorodecyltrichlorosilane (FDTS) in a molecular vapor deposition system.[2, 3] The thinner wafer (50-um) was designed with holes as the substrate for in-situ x-ray diffraction (XRD) of protein amyloid fibrils. Around 6 uL protein amyloid fibrils solution was dropped on the SHS and evaporating on temperature controlled hot-plate at setting temperature gradient (i.e., the differences between hot-plate and ambient temperature).[4] The in-situ and real-time movements of amyloid fibrils generated from hen egg white lysozyme molecules driven by the optimized confined convective flow were acquired. For the first time these images showed the direct evidence that flow field induced the amyloid fibrils aggregation. Two-dimensional X-ray diffraction and laser confocal Raman analysis of these deposits indicated that their secondary structures is a mixture of alpha-helix, beta-sheet and disordered polypeptide chains. [1] Eur. J. Med. Chem. 139 (2017) 153-16 [2] Sci Adv. 1(7) (2015) e1500734. [3] Nat. Photonics 5(11) (2011) 682-687. [4] J. Phys. Chem. B 110(14) (2006) 7090-7094

Resume : Investigation of the spectral characteristics of individual bioobjects, in particular, protein complexes of potatoes susceptible to Cancer Synchytrium Endobioticum (Schilbersky) Percival, is a rather complicated task. This is due to the fact that the individual characteristic oscillations of the molecular complexes are located in the middle of the visible and near-infrared wavelength range. The presence of a natural electromagnetic background and combinational frequencies from close-to-structure complexes leads to the blurring of the main lines of the spectrum of the substances being studied. Therefore, the purpose of this work was to create mathematical models and corresponding software to enhance the resolution of the molecular spectroscopy technique used. The basis of the proposed model is the use of differential methods both at the stage of measuring the information signal, and at the stage of its mathematical processing. The application of the Fast Fourier Transform method and the numerical analysis of numerical series allows one to differentiate the investigated spectra with a resolution of 1-2 nm. The software for the hardware implementation of the method, as well as for time-differentiated data analysis, which allows, in addition to qualitative identification of the spectrum lines, to carry out a semi-quantitative analysis of components with an accuracy of 8-10% are designed.

Resume : Multimodal agents are gaining a worldwide spread interest due to their diagnostic and therapeutic (theranostic) feasibility in cancer treatment. Photothermal therapy (PTT) is the latest, localized approach to cancer therapy. It utilizes nanoparticles which can transform absorbed light, usually in the infrared (IR) region, into the heat inside a living cell leading to cell death. Here we present synthesis and characterization of new hybrid bioinspired nanomaterials based on polydopamine and fluorescent nanodiamonds capable of simultaneous PTT and imaging. In our approach first, we developed a method to control the size of the polydopamine particles in a range from 40 to 200 nm. As obtained nanoparticles were modified to introduce carboxylic groups that further are used to attach well-dispersed fluorescent nanodiamonds (fNDs). This method allows avoiding the fluorescence quenching by PDA , provide excellent biocompatibility and high photothermal response. Additionally, the introduction of metal ions into such a system is discussed. In summary, an effective protocol for a preparation multifunctional nanoparticles for combined PTT and imaging technique, comprised of known biocompatible components is introduced with high potential application in nanomedicine.

Resume : Natural plant structures such as spines of cacti and trichomes of pitcher plants can effectively harvest and rapidly transport water to survive harsh environment. Inspired by these structures, conical shapes with structural gradient in micro and nano scales have been studied to enhance directional water transport from tips of plants where water is collected to their body. The objective of this study was to introduce a bioinspired conical microfiber with a grooved cross-section along circumferential direction and gradient groove curvature from concave at the tip to convex in the body. Conical microfibers with concave cross-section were fabricated using an atmospheric pressure plasma treatment through asymmetric etching of undulated geometry. Under plasma treatment condition with gas fraction of Ar and O2 and plasma power, the fiber was etched fast near the tip but late on body region, resulting in a conical shape at the tip with apex angle ~ 5 to 10 deg. The diameter of the conical microfiber gradually increased from 500 nm~2 μm at the tip to 10~20 μm around the body. Simultaneously, gradient cross-section along the axial direction was also achieved through asymmetric etching between valley and peak of the convex cross-section. Such conical fiber showed strong directional water transport, sending harvested water at the tip from fog toward the body. ESEM observation showed that water was formed as film-wised condensation in concave grooves of the conical fiber. The velocity of the condensed water on the conical tip was measured to be as fast as 800 μm/sec while it was very slow on the fiber body. Water collecting efficiency of conical structures was also evaluated and discussed at single fiber level as well as for a bundle of conical fibers assembled in helical way.

Resume : Our work addresses the problem how to prepare specific protein based sensor layers for arsenic detection in water. Bacterial flagellar filaments, composed of thousands of flagellin variant subunits, were used as scaffolds of specific arsenic binding peptide sequences. As-binding flagellin variants were constructed by optimization of the length of the As-binding oligopeptide motif inserted into flagellin. As it has been proven, these fusion proteins retain polymerization ability. Golden working electrodes for electrochemical sensing were prepared on silicon wafers using standard physical vapor deposition and standard lithography methods. Flagellar nanotubes composed of As-binding flagellin variants were deposited onto the surface of working electrodes using wet chemical deposition. The coverage of the working electrode was verified by SEM microscopy. Cyclic voltammetry was applied to detect the presence of As in aqueous solutions. Measurements were performed at pH=7.0 (100 mM HEPES, 150 mM NaCl) using -0.6 – +0.6V potential range vs. saturated calomel electrode. Our experiments showed that controlled addition of arsenic into the solution causes a current peak in the voltammogram correlating with the increasing arsenic concentration. The peak was observable at 0.01mg/L concentration (i.e. at the threshold limit for As in drinking water). The binding of As to the protein was also detected by independent methods (i.e. ellipsometry and ITC). These results form the basis of a portable analytical tool for quick arsenic detection in natural waters and ground water. Support from the M-ERA.NET-VOC-Detect/2019, OTKA NNE 131269 and K115852 projects is greatly acknowledged.

Resume : Silicon quantum dots (SiQDs) are highly photoluminescent semiconductor nanoparticles that continue to attract interest as promising materials for medical diagnostics and chemical/biological sensing. Their biocompatibility and nontoxicity make them an attractive alternative to the more popular but cytotoxic cadmium-based quantum dots for biological applications. Elastin-like polypeptides (ELPs) are biological polymers that have chemical structures based upon the mammalian protein elastin. They undergo reversible phase transition and assemble into nanoscale and microscale structures in response to changes in temperature, pH, and ionic strength, among others. We report herein the preparation of hybrid materials from SiQDs and ELPs through the amide coupling reaction. Successful conjugation of ELPs to the SiQDs was confirmed through Fourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The hybrids retain the characteristic intense orange photoluminescence and microsecond excited state lifetimes of the SiQDs and the thermal responsiveness of the ELPs. They form photoluminescent microscale assemblies upon heating, which then dissociate back into individual nanoparticles upon cooling, as confirmed by dynamic light scattering analysis. The hybrids prepared herein offer an attractive platform in biomedical and sensing applications where spatio-temporal control over probe behavior is of paramount importance.

Resume : Presently, cardiovascular disorders are still among the main causes of death in developed countries [1]. Ischemic heart disease and arterial hypertension occupy leading positions in the list of nosological factors leading to lethal outcomes, followed by calcifiic aortic stenosis—a pathology of old and advanced age that is becoming more and more topical because of the general increase in the average lifetime. Morphologically, calcific aortic stenosis is characterized by the deposition of hydroxyapatite crystals in aortic valve demilunes, which leads to irreversible violations of their structure and function [2,3]. At present, there are no effective methods for primary or secondary prophylaxis of this acquired disorder. We have studied X-ray diffraction (XRD) patterns of calcinates isolated from aortic demilunes of patients with calcific aortic stenosis. It is shown that the observed XRD pattern is formed by spherical formations of hexagonal hydroxyapatite with diameters distributed according to the lognormal law. A model of the structure of these formations is constructed and the possible mechanisms of their nucleation and encapsulation of hydroxyapatite particles in the restricted porous space of the basal membrane of aortic valve demilunes are discussed. We've also created the simple in vitro chemical model of the early stages of the mentioned disease as well as computational model of the hydroxyapatite nanoclusters. 1. R. C. Li, A Research Report, Document No. 227502 (U. S. Department of Justice, 2009). 2. N. I. Gulyaev, M. V. Zhukov, G. L. Kuranov, Yu. A. Borisov, E. D. Suglobova, S. G. Yastrebov, and A. S. Peleshok, Ul’yanovsk. Med.-Biol. Zh., No. 1, 23 (2017). 3. T. Ida, S. Shimazaki, H. Hibino, and H. Toraya, J. Appl. Crystallogr. 36, 1107 (2003).

Resume : The aim of this study was to obtain a biocompatible nanostructured scaffolds based on chitosan nanospheres loaded with silver nanoparticles with dual functions, namely promoting wound healing and long-lasting antibacterial effectiveness toward various types of bacteria. Chitosan was chosen due to the influence that it has in various steps of complex wound healing process and due to ability to depolymerize into N-acetyl-d-glucosamine, which start the fibroblast proliferation, facilitating in ordered collagen deposition and stimulates increased levels of natural hyaluronic acid synthesis at the wound site. Physico-chemical evaluations were performed by using the thermogravimetric analysis (TGA), scanning electron microscopy (SEM) transmission electron microscopy (TEM) and fourier transform infrared spectroscopy (FTIR). In vitro biocompatibility was tested using endothelial human cells (fluorescence microscopy and proliferation assay), while in vivo studies were performed on a rat burn wound experimental model. Results demonstrated the capacity of prepared nanostructured scaffolds to accelerate wounds healing along with a good antibacterial effect.

Resume : We selected the thin films with self-assembled layers of fullerene C60/C60 oxygen derivatives/ds-DNA on silicon for the detail investigations due to their conductivity – photosensitivity in designed Chip. The evidence of self-assembling of these layers with (ds-DNA) in the molecular films on silicon oxide surface were obtained on the base of STM and SEM images of the films with the assembles (8-10 and 30-40 nm in diameter). The molecular structures with conductive interfaces - conductivity of the films was modulated by diode characteristics of fullerene C60/6-5 open fullerene C60 and C60/ ds-DNA contacts for n-type semiconductors fullerenes what were determined by STP - tunneling spectroscopy. The discovered dynamic behavior of photosensitivity to 200-400 nm irradiation under (0,25-0,37 eV) at 400-1000 nm irradiation (during 10 min - 1 h) of these films with several molecular structures allow to consider these supramolecular layers/films as conductive/ photovoltaic chip.

Resume : Ti-based alloy, Co-Cr alloy, and stainless steel alloy were mainly used as implant material in orthopedic surgery, even though subsidiary surgery must be needed to remove them later. To give accommodation to the patient, Mg-based implant material is actively investigated these days since Mg-based material has high degradability and induces bone formation in the human body so that additional implant-removal surgery could be skipped. In this study, Mg-5Ca-1Zn alloy was prepared to complement the low mechanical property of Mg and contribute to the bone recovery by a residual Ca and Zn. Furthermore, we conducted anodic oxidation using Mg-5Ca-1Zn alloy to improve the corrosion resistance by the formation of the oxide film on the surface of the alloy. Experiments were carried out at various voltage and time conditions. Consequently, we could fabricate the MgO layer on the surface successfully as a decomposition-retardant of Mg alloy. By analyzing the surface morphology using FE-SEM, the surface of the oxide film had pores with small diameter, and the number of pores was influenced by experimental conditions. Besides, the thickness of the oxide film tends to increase with increasing voltage application time, showing an unremarkable difference after 20 min.

Resume : Recently the growing interests in natural systems have driven materials design through bio-inspired routes, and have led to high performance in applications such as environmental catalysis and energy conversion/storage system. Among these, aprotic lithium-oxygen (Li-O2) batteries are promising because of their high theoretical energy density, which arises based on the spontaneous oxidation of Li on the anode and reduction of O2 at cathode to form Li2O2. However, the aprotic electrolyte used in these batteries has low O2 diffusivity and the solid discharge product, Li2O2, hinders O2 transportation within the cathode. Inspired by natural O2 transportation in mammals, we propose in this research using biomolecules as oxygen carriers for aprotic Li-O2 battery. Our hypothesised advantage with this approach is that O2 transport will be improved to increase the reaction are, thereby improving the electrochemical performance in terms of capacity as well as reversible cycles. In this contribution, we present our results on how we mimic the mammalian metabolic system in batteries using natural oxygen carriers, and how different oxygen-carrying molecules and electrolytic environments affect the battery performance.

Resume : One of the latest trends in the fields of tissue engineering as well as oncological research is the development of in vitro 3D systems mimicking the target tissue or organ. Indeed, there is an increasing demand for in vitro models recapitulating the tridimensional structure and microenvironment experienced by cells in vivo. This approach has manifold applications in fields such as basic research, drug discovery, tissue engineering, offering a valid alternative to the use of animals in testing. Interestingly, certain tissues are known to be regulated by endogenous bioelectrical cues, in addition to chemical and mechanical cues. One such tissue is bone. Moreover, electrical stimulation has been proven to support cell proliferation as well as to boost the expression of genes related to stem cells osteogenic differentiation. We report on the development of electroactive scaffolds based on the conducting polymer PEDOT:PSS. Blends of PEDOT:PSS and Collagen type 1 were used to prepare macroporous scaffolds. These macroporous substrates were used for stem cell culture and osteogenic differentiation. First experiments of stem cell differentiation via electrical stimulation were run and some preliminary results will be discussed. Porous conductive scaffolds are a valuable in vitro platform for the development of 3D models for the study of stem cell response to electrical stimulation for bone tissue engineering.

Resume : Fullerene derivatives previously demonstrated a diverse spectrum of antiviral activities against such viruses as herpes simplex virus, cytomegalovirus, human immunodeficiency virus, hepatitis C virus, Ebola-related viruses and influenza viruses. Therefore, they can be considered as a promising group of compounds for designing antiviral drugs. Here we present a new family of water-soluble fullerene derivatives with five amino acid residues attached to the carbon cage around one cyclopentadienyl rings. The application of amino acid solubilizing groups ensures biocompatibility of the designed compounds. All fullerene derivatives were synthesized from chlorofullerene C60Cl6 as a precursor and characterized by NMR spectroscopy and mass spectrometry. Additionally, the aggregation behavior of the compounds in aqueous solutions was explored using dynamic light scattering. The designed amino acid fullerene derivatives showed low cytotoxicity and acute toxicity in mice (LD50 of 500-900 mg/kg) and demonstrated promising antiviral activities against a broad range of viruses such as herpes simplex virus, human immunodeficiency virus and influenza viruses. The best compounds outperformed significantly commercial anti-influenza drugs such as oseltamivir carboxylate (Tamiflu®) and zanamivir (Relenza®) tested under the same conditions. Thus, low toxicity and strong antiviral action of amino acid fullerene derivatives makes them promising drug candidates for suppressing viral infections.

Resume : Worldwide, millions of patients are affected annually by healthcare-associated infection (HCAI), impacting up to 80,000 patients in European Hospitals on any given day. This represents not only a public health risk, but also an economic burden. Through its Cooperation in Science and Technology programme (COST), the European Commission has recently funded a four-year initiative to establish a network of stakeholders involved in development, regulation and use of novel antimicrobial coatings for prevention of HCAI. The AntiMicrobial Coating Innovations (AMiCI) network currently comprises participants of more than sixty universities, knowledge institutes and companies across twenty-nine European countries and, to date, represents the most comprehensive grouping to target use of these emerging technologies in healthcare settings. By accessing the network?s website (www.amici-consortium.eu), there is an ongoing opportunity for those interested to engage with the program. Infections and infectious diseases are considered a major challenge to human health in healthcare units worldwide. AMiCI recognizes, and aims to address, the disparate perspectives of inventors and entrepreneurs; academic researchers; manufacturers; distributors; commercial, clinical, biocide and consumer affairs regulators; medicines agencies; clinical microbiologists; attending physicians; healthcare facility managers and procurement officers; environmental monitoring specialists and environmental protection agencies; hygiene companies; and, of course, patients and their carers. The AMiCI consortium is addressing this challenging diversities of viewpoints through a series of consultation events and targeted transfer of personnel between industry and academic groups, strategically chosen to deal with the most pressing topics arising from those consultations, and development of coating capable of demonstrably reducing HCAI. The AMiCI network focuses on scientific information essential for weighing the risks and benefits of antimicrobial surfaces in healthcare settings. Particular attention is drawn to nanomaterial-based antimicrobial surfaces in frequently-touched areas in healthcare settings and the potential of these nano-enabled coatings to induce (eco)toxicological hazard and antimicrobial resistance. Possibilities to minimize those risks, e.g. at the level of safe-by-design, are demonstrated.

Resume : Osteoarthritis (OA) is a progressively degenerative disease that is accompanied by articular cartilage deterioration, sclerosis of the underlying bone and ultimately joint destruction. Although therapeutic medicine and surgical treatment are done to alleviate the symptoms of OA, it is difficult to restore normal cartilage function. Mesenchymal stem cell (MSC) transplantation is one of the therapeutic trials for treating OA due to its potential, and many researchers have recently reported on the effects of MSCs associated with OA therapy. However, cell transplantation has limitations including low stem cell survival rates, limited stem cell sources and long-term ex vivo culturing. In this study, we evaluated the efficacy of neuropeptide substance P coupled with self-assembled peptide hydrogels in a rat knee model to prevent OA by mobilizing endogenous MSCs to the defect site. To assess the effect of the optimal concentration of SP, varying concentrations of bioactive peptides (substance P (SP) with self-assembled peptide (SAP)) were used to treat OA. OA was induced by unilateral anterior cruciate and medial collateral ligament transection of the knee joints. Forty rats were randomly allocated into 5 groups: SAP-0.5SP (17.5 mg of SP), SAP-SP group (35 mg of SP), SAP-2SP group (70 mg of SP), SAP-SP-MSC group, and control group. At 2 weeks post-surgical induction of OA, each mixture was injected into the joint cavity of the left knee. Histologic examination, immunofluorescence staining, quantitative real time-polymerase chain reaction and micro-computed tomography analysis were done at 6 weeks post-surgical induction. As shown by our results, the SAP-SP hydrogel accelerated tissue regeneration by anti-inflammatory modulation shown by an anti-inflammation test using dot-blot in vitro. Additionally, the treatment of OA in the SAP-SP group showed markedly improved cartilage regeneration through the recruitment of MSCs. Thus, these cells could be infiltrating into the defect site for the regeneration of OA defects. In addition, from the behavioral studies on the rats, the number of rears significantly increased 2 and 4 weeks postinjection in all the groups. Our results show that bioactive peptides may have clinical potential for inhibiting the progression of OA as well as its treatment by recruiting autologous stem cells without cell transplantation.

Resume : A biosensor based on gelatin composite biopolymers nanofibers is found to be effective in identifying physical influences. Biopolymer nanofibers were made by electrospinning method. After optimizing the synthesis parameters, nanofibers biopolymers were obtained, averaged 50-100 nm in diameter, and then modified on the surface of the working electrode. Effect of the intensity of the transducer buffer and the working potential of the current response. The nanofilament-modified electrode to the temperature is optimized to obtain the maximum current response [1]. Effect of the intensity of the transducer buffer and the working potential of the current response. The nanofilament-modified electrode to the temperature is optimized to obtain the maximum current response. The results revealed that the temperature of the gelatin composite biopolymer nanofibers had the advantages of rapid reaction, excellent reproducibility, high stability and showed a nonlinear reaction in the dynamic range from 273 K to 373 K with a detection limit of 0.1 K and a high sensitivity of 10 µA·mM?1· cm?2. The proposed strategy based on gelatin composite biopolymer nanofibers can be extended for the development of other enzyme-based biosensors. [1] O.Dubok, O.Shynkaruk, E.Buzaneva, Lanthanides oxides usage to increase radiopaque of bioactive ceramics, Funct. Mater. 2013; 20 (2): 172-179. http://dx.doi.org/10.15407/fm20.02.172

Resume : Graphite is composed of layers of linked carbon hexagons. Between the layers, base metals such as potassium and the like, but also metal compounds can be incorporated, forming new substances (GIV). In high-temperature electrolyses any GIV formed may destroy the carbon electrodes. In other processes, such as the production of graphite foils, a versatile material with outstanding chemical and physical properties, make GIV the crucial intermediate. The electrochemical behavior of GIV opened up the possibility of constructing new high-performance lithium-GIV battery systems. New carbon compounds are found and their reaction behaviour characterized [1]. In addition to graphite and diamond, the group of fullerenes is the third carbon form, which has been experimentally accessible by graphite evaporation in the carbon arc. In the case of graphite evaporation, in addition to the fullerenes, similarly constructed carbon tubes. Buckminsterfullerene is soluble in organic solvents and gives a brownish product in the solid state. Fullerenes with many inorganic and organic substances react to form derivatives that have interesting physical properties and potential applications in the field of superconductivity and nonlinear optics. Fullerene research is an area of research in chemistry, materials science, physics and medicine. [2]. Considering of CNTs, our research is focused on the study of CNT synthesis and growth mechanisms upon thermal chemical vapour deposition, and their electrochemical properties. The functionalization of CNTs, through a chemical attachment of either molecules or functional groups to their sidewalls, is an effective way to improve their solubility and to enhance their physical properties that make them of potentially useful for technological applications ranging from nanoelectronics, sensors and electrochemical devices to composite materials. Graphene is the carbon fourth form: the 2D material graphene, made of carbon atoms arranged in a honeycomb lattice, has its peculiar mechanical, electronic, optical, and transport properties. Many of these features result solely from the symmetry properties of the honeycomb lattice. The chemical modification can be achieved via either covalent or non-covalent interactions. Covalent modifications often destroy some of the graphene conjugation system, resulting in compromising some of its properties.[3]. 1. Gupta, Vinay; Scharff, Peter; et al., C60 intercalated graphite: a new form of carbon. - In: Fullerenes, nanotubes & carbon nanostructures : An international and interdisciplinary journal.: Taylor & Francis, 13.2005, Suppl. 1, S. 427-430, http://dx.doi.org/10.1081/FST-200039421 2. H.M. Kuznietsova, O.V. Lynchak, N.V. Dziubenko, V.L. Osetskyi, O.V. Ogloblya, YuI. Prylutskyy, V.K. Rybalchenko, U. Ritter, P. Scharff, Water-soluble C60 fullerenes reduce manifestations of acute cholangitis in rats // Applied Nanoscience (2018), P.1–8, DOI: 10.1007/s13204-018-0700-5 3. Szroeder,PawełTsierkezos, Nikos G.; Walczyk, Mariusz; Strupi´nski, Włodzimierz; Górska-Pukownik, Agnieszka; Strzelecki, Janusz; Wiwatowski, Kamil; Scharff, Peter; Ritter, Uwe, Insights into electrocatalytic activity of epitaxial graphene on SiC from cyclic voltammetry and ac impedance spectroscopy. - Journal of Solid state electrochemistry: current research and development in science and technology. - Berlin : Springer, 18 (2014), 9, 2555-2562, http://dx.doi.org/10.1007/s10008-014-2512-1

Resume : Thanks to the excellent physical and chemical properties, nano-scale carbon materials with different dimensions and unique novelties have been proposed for a number of applications for our life, such as biomedicine, electronics, catalysts, energy storage and so on. In fact, the performance of carbon nanomaterials signifcantly depends upon their versatile electronic structures and microstructures. These can be precisely tailored by rational defect engineering, heteroatom doping, heterostructure coupling, etc. Meanwhile, prompted by the blossoming research in two-dimensional (2D) graphene, many attentions have been focused on new 2D layered-structure materials. By integrating carbon-based supports, such as graphene, activated carbon, carbon nanotube, will be beneficial to 2D layer’s charge transfer or well dispersion because of the high surface to volume ratio and excellent chemical stability of carbon materials. Herein, I will present our recently studies on the design and relazation of promising nano-structured materials, via tolaring and intergrating various dimensional carbon materials. We hope, such integration may open a window for futher exploring the multifunctional applications of nanocarbons in many specific fields. (ABSTRACT for KEYNOTE LECTURE)

Resume : Multilayer graphene (MLG) has been actively investigated because of its high electrical and thermal conductivities. Because graphene has a unique two-dimensional structure, its characteristics are anisotropic. Therefore, large-grained highly oriented MLG on insulators is highly desirable. Metal-induced layer exchange (MILE) is a promising technique allowing for large-grained, highly-oriented Ge and Si on glass [1]. In this study, we applied MILE to amorphous carbon (a-C) and fabricated high-quality MLG at as low as 500 °C. Ni and a-C thin films (each 50 nm thick) were sequentially prepared on glass using magnetron sputtering. Samples were annealed at 500 °C for 50 h. The Ni layers were then etched away. The Raman spectra of back side of the samples have sharp D, G, and 2D peaks corresponding to MLG, indicating the layer exchange between the C and Ni layers [2-4]. The cross-sectional TEM analyses showed the layers of a-C and Ni were exchanged and {002} oriented MLG formed on glass substrate. The grain size was several hundred nm. After the removal of the Ni layers, the MLG covered the entire substrate. The electrical conductivity was approximately 400 S/cm. The uniformity and electrical conductivity are the highest level among the MLG directly formed on glass at low temperature. Furthermore, annealing in the sputtering chamber immediately after deposition of the films resulted in MLG formation below the softening temperature of polyimide substrate (< 400 °C). These achievements open up the possibility for developing flexible graphene devices. [1] Toko et al., APL. 104, 022106 (2014). [2] Murata et al., APL. 110, 033108 (2017). [3] Murata et al., APL. 111, 243104 (2017). (Highlighted in Nature INDEX.) [4] Murata et al., Sci. Rep. 9, 4068 (2019).

Resume : We present an overview of our studies on the synthesis and investigation of water-soluble fullerene derivatives (WSFs). Chlorofullerenes C60Cl6 and C70Cl8 were shown to be ideal precursors for synthesis of various WSFs. Friedel-Crafts type reactions led to big families of C60 and C70 derivatives bearing appended fragments of arylalkylcarboxylic and aryloxyalkylcarboxylic acids [Org. Biomol. Chem., 2019, 10.1039/C9OB00593E, Chem. Commun., 2011, 47, 8298]. Novel reactions with amines, amino acids [Chem. Commun., 2012, 48, 5461], thiols, thioacids [Chem. Commun., 2012, 48, 7158; Tetrahedron Lett. 2016, 57, 1215], trialkylphosphites [Chem. Commun., 2012, 48, 8916; Tetrahedron Lett. 2016, 57, 5570], and alcohols [Org. Biomol. Chem., 2017, 15, 773; Tetrahedron Lett., 2017, 59, 605] produced new classes of WSFs. Toxicity and different types of biological activity of the prepared WSFs will be discussed. A particular attention will be paid to antiviral activity. It is commonly believed that anti-HIV action of WSFs is related to the HIV protease inhibition. We will prove with many examples that this belief is not correct in many cases and WSFs actually inhibit multiple other HIV targets. Moreover, examples of WSFs demonstrating impressive activity against influenza, herpes simplex virus, cytomegalovirus, etc. confirm great potential of using water-soluble nanocarbon materials in biomedicine and drug design.

Resume : One of the most fascinating carbon allotropes is the diamond. Discovered in the nineteen-sixties nanodiamonds (NDs) area nanoscale version of the fascinating gems. Due to their inherent properties, NDs have attracted the interest of researchers in recent years. They exhibit low genotoxicity and cytotoxicity in comparison to the questionable biocompatibility of CNTs, It was also demonstrated that they do not have any toxic effect on brain cells when they were used for imaging. Furthermore, the functional groups present on the surface of NDs allow facile conjugation of biological moieties such as proteins, DNA, RNA or drugs. Therefore, they pose a tremendous opportunity to develop a new family of NPs for cancer treatment. In this report, we present our research regarding coating nanodiamonds with biocompatible polydopamine that vest them photothermal properties and their application in photothermal therapy of glioblastoma multiform in vitro. The research was financed under by The National Science Centre, Poland under project number 2016/21/B/ST8/00477.

Resume : The potential use of stem cells in regenerative medicine requires the ability to be able to control stem cell fate as cellular networks are developed. Here, nanodiamonds (~10nm) are supported on glass and shown to be an excellent host for the attachment and proliferation of human neural stem cells. Moreover, it is shown that spontaneous differentiation into neurons occurs on nanodiamonds. The use of variously oxygen terminated and hydrogen terminated nanodiamonds has been explored. It is shown that O–ND monolayers promote the differentiation of hNSCs into neurons with increased total neurite length, degree of branching and density of neurites when compared with H–NDs or the glass control. The total number of neurites and total neurite length expressing MAP2, a protein enriched in dendrites, was over 5 times higher for spontaneously differentiated neurones on the O–NDs compared to the control. The fact that inexpensive nanodiamonds can be attached through simple sonication from water on 2D and 3D shapes indicates significant promise for their potential as biomaterials in which neuro-regenerative diseases can be studied.

Resume : Nanomedicine is attracting growing interest in terms of targeting cancer theranostics. Since the concept of our research is to “apply organic chemistry to nanomaterials”, we have been trying to functionalize and construct nanomaterials for biomedical purposes. In this talk, I would like to introduce our recent subjects about the application of nanomaterials for cancer diagnosis and therapy from the two opposite aspects of “hard” and “soft”; 1) functionalization of nanodiamonds as a drug carrier and a cancer fluorescence imaging agent [1], and 2) construction of metal-free magnetic mixed micelles as a MR imaging agent and a drug carrier [2]. [1] L. Zhao, N. Komatsu, X. Chen, et al., Adv. Funct. Mater., 24, 5348 (2014) [highlighted at the inside front cover]; L. Zhao, N. Komatsu, X. Chen, et al., Biomaterials, 35, 5393 (2014); T.-F. Li⁠⁠, N. Komatsu, L. Zhao, X. Chen, et al., Biomaterials, 181, 35 (2018). [2] K. Nagura, N. Komatsu, R. Tamura, et al., Chem. Eur. J., 23, 15713 (2017); K. Nagura, N. Komatsu, R. Tamura, et al., Nanotechnology, 30, 224002 (2019); K. Nagura, N. Komatsu, R. Tamura, et al., Pharmaceutics, 11, 42 (2019).

Resume : Thermal sensing is a key technique to understand the heat production in cells, thus many kinds of fluorescence-based nanothermometers have been developed, e.g., quantum dots, rare-earth metal complexes, polymers and genetically-encoded proteins. Indeed, several research groups have discovered markedly high temperature inhomogeneity (> 1 °C) inside a single cell by using these thermometers. Since there is a possibility that the inhomogeneity contributes to a torque for certain biological reactions, scientists have started to unveil the biological significance of the inhomogeneity of temperature in cell. In this presentation, we first report that thermosensing ability of FNDs is hardly influenced by pH, ion concentration, viscosity, molecular interaction, and organic solvent. We have experimentally proved for the first time that the robustness against environmental factors renders FND as an ideal temperature sensor inside single cells. We further present a simple protocol to measure absolute temperature inside a cell. In the protocol, magnetic resonance signal was first obtained from live cell, followed by cells fixation using ethanol, then calibration lines from identical FNDs were obtained. This technique is simple but enables absolute temperature measurement in single cells within the accuracy of ±1 °C.

Resume : Although considerable research has been conducted on the use of 2D materials as drug delivery systems, very little is still known about the subsequent fate of the carrier. The design of smart multifunctional materials able to both selectively deliver a drug into cells in a targeted manner and display an enhanced propensity for biodegradation is crucial. Here, graphene oxide (GO) is functionalized with the chemotactic peptide N-Formyl-Methionyl-Leucyl-Phenylalanine (fMLP) known to interact with the formyl peptide receptor, which is expressed in different cancer cells, including cervical carcinoma cells. This study highlights the ability of GOfMLP for targeted drug delivery and cancer cell killing and the subsequent degradation capacity of the hybrid. We demonstrate that GOfMLP is susceptible to a faster myeloperoxidase mediated degradation. The hybrid material, but not GO, is capable of inducing neutrophil degranulation with subsequent degradation, being the first study showing inducible neutrophil degradation by the nanomaterial itself with no prior activation of the cells. Moreover, confocal imaging and flow cytometry using HeLa cells show that GOfMLP is able to deliver the chemotherapeutic agent doxorubicin faster into cells, inducing higher levels of apoptosis, when compared to non-functionalized GO. Overall, this work reveals that GOfMLP is a promising carrier able to efficiently deliver anti-cancer drugs, being endowed with the capacity to induce its own biodegradation.

Resume : Polydiacetylenes are mechanochromic polymers, that show a change (e.g. chromism, fluorescence, electrical properties (1) etc.) upon external stimuli such as heat, stress or changes in chemical environment (2, 3). However, how these stimuli influence their structure (4) and how that relates to their optical properties is still not clear to this day. To address these questions, we deposited 10,12-tricosadiynoic acid onto plasma-activated glass substrates, exposed to UV for polymerisation, and applied forces to the polymerised film by an atomic force microscope, while simultaneously measuring the emitted fluorescence. The fluorescence is characteristic of the transformed red phase of polydiacetylenes, thus enabling us to follow the phase transition, while the atomic force microscope registers the forces exerted to the polydiacetylene chains. Combining the two techniques could open a path to the fluorescence – force calibration of the colour change, contributing to a deeper understanding of polydiacetylenes. 1. Girard-Reydet C, Ortuso RD, Tsemperouli M, Sugihara K. Combined Electrical and Optical Characterization of Polydiacetylene. J Phys Chem B. 2016;120(14):3511-5. 2. Wen JT, Roper JM, Tsutsui H. Polydiacetylene Supramolecules: Synthesis, Characterization, and Emerging Applications. Ind Eng Chem Res. 2018;57(28):9037-53. 3. Ortuso RD, Cataldi U, Sugihara K. Mechanosensitivity of polydiacetylene with a phosphocholine headgroup. Soft Matter. 2017;13(8):1728-36. 4. Ortuso RD, Ricardi N, Burgi T, Wesolowski TA, Sugihara K. The deconvolution analysis of ATR-FTIR spectra of diacetylene during UV exposure. Spectrochim Acta A Mol Biomol Spectrosc. 2019;219:23-32.

Resume : In this tutorial lecture, I will discuss the developments of the surface nanostructured materials in our group and their applications for the isolation of circulating tumor cells (CTCs) and circulating fetal trophoblasts as noninvasive diagnostic tools. We have fabricated various nanostructured on different materials including silicon, PDMS, photocurable polymers and conducting polymers. We have found that the cell adhesion increased with the surface roughness, which can be correlated to the increase in the density of focal adhesion molecules on the nanostructures with smaller sizes. Taking advantage of the enhanced cell adhesion on the nanostructured surfaces, we have designed a rare cell isolation system using nanostructured materials. In a recent study, we have 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). We have demonstrated that these nanofiber 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 every 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 the 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. At the end, I will discuss the drug releasing capability of our device, which may allow us to conduct on-chip drug screening for the isolated CTCs.

Resume : Accurate measurement of tissue properties becomes more and more important not only in biomedical applications such as diagnostic imaging for tissue pathology but also for designing novel bio-mimetic materials for tissue engineering. Optical coherence tomography (OCT) is a three-dimensional non-invasive optical imaging technique, which has been extensively used to characterize depth-resolved tissue properties such as birefringence, absorption, anisotropy, scattering, and stiffness. These properties can be used in designing novel bio-mimetic materials for tissue engineering. During this talk, the basic working principle of an OCT system, different OCT types, and how to incorporate them in characterization of tissue properties will be discussed. In addition to commonly used OCT systems, I will discuss two functional OCT systems; i.e. polarization sensitive OCT and OCT vibrography, in characterization of tissue properties. For probing regional tissue properties inside the human body, endoscopic OCT system will also be covered.

Resume : In last decade the smart hybrid nanostructures (SHN) has been proposed for the theranostic of different types of human tumors. This include the technologies that enable simultaneous diagnosis, primary and if necessary secondary treatment as well as monitoring of the therapy outcomes. The SHN can be administrated directly or indirectly into the tumors and respond to different external physical stimuli such as ultraviolet, visible or near-infrared light, radiofrequency waves, X-ray, alternating magnetic field or ultrasound waves. Among of all SHN a special interest gain the nanocomposites that may be stimulated by light and used as remote triggers to exert anti-tumor activity through irradiation. Nowadays, the light-mediated cancer theranostic more often applies near infrared (NIR) radiation than ultraviolet (UV) or visible light (VIS) which is connected with greater and deeper NIR penetration into the tissues and its smaller scattering, however the exact light used depends on the type of the nanomaterial and therapeutic modality. The light-stimulated nanotheranostics are usually combined with different types of therapies like photodynamic therapy (PDT), photothermal therapy (PTT), photo-triggered chemotherapeutics (PTCH) or two-photon triggered therapy (TPTT). They are commonly integrated into one single multifunctional nanoplatform, that often may use different light triggered co-therapy modalities by designing smart multifunctional materials which combine the different types of imaging and therapeutic agents. Recently, many new strategies are developed to increase the overall therapeutic effect of SHN like eg. oxygen self-enriching photodynamic therapy (Oxy-PDT) where the photosensitizer is stuffed into perfluorocarbon nanodroplets to optimize tumor oxygenation or decorating platinum nanozymes on photosensitizer integrated metal organic frameworks (MOFs) to enhance PDT. Also new ways of increasing light penetration into the tissues are testing such as wireless photonic activation that enables on-demand light excitation of photosensitizers for therapeutic dosimetry. On the contrary, in case of fragile human organs a wireless systems for metronomic cancer treatment (long-term low-dose PDT) are proposed to offer an alternative way of tumors treatment. In case of clinically demonstrated SHN-based photothermal therapy, so far the photothermal transduction agents (PTAs) were mainly design to respond to the NIR-I (700-950nm) and NIR-II (1000-1350 nm) widows. Lately, the innovative optical technologies that provide more efficient light penetration into deeply located tissues with much less attenuation using new transparency regions NIR-III (1600-1870nm) and NIR-IV (2100-2300 nm) were reported. Reassuming, the current generation of light-mediated tumor theranostic strategies seek to strengthen both, therapy and diagnosis by using multifunctional smart hybrid nanostructures coupled with minimally invasive biomedical devices that maximize both, the permeability of the drug to the tumor and penetration of light. Acknowledgements The project leading to this work has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement No 751903.

Resume : Keywords: cancer, theranostics, nanoparticles, ultrasmall, photothermal Plasmonic noble metal nanoparticles (NPs) have attracted increasing interest for their potentiality to revolutionize diagnosis and treatment of many diseases, especially neoplasms.1,2 Nonetheless, there are still no clinically approved NPs for cancer therapy/diagnostic and very few candidates are in clinical trials. The clinical translation of NPs is mainly prevented by their persistence in organism after the medical action. Such persistence increases the likelihood of toxicity and the interference with common medical diagnoses. Size-reduction to ultrasmall nanoparticles (USNPs) is a suitable approach to promote metal excretion by the renal pathway, however altering most of the behaviors of NPs.1 A groundbreaking advance to jointly combine the appealing features of NPs with metal excretion relies on the ultrasmall-in-nano approach.1 Within this approach, we have designed inorganic all-in-one biodegradable nano-platforms comprising plasmonic USNPs: the nature-inspired passion fruit-like nano-architectures (NAs).3,4 The versatility of NAs production will be presented, together with the significant metal-excretion trend from murine models and preliminary applications, in particular for photothermal treatments.5–8 Furthermore, the last achievements from this novel approach will be discussed and the next exciting perspectives provided. Such nano-architectures might bring again noble metal nanomaterials to the forefront of cancer theranostics, in order to treat carcinomas in a less invasive and more efficient manner. The research leading to these results has received funding from AIRC under MFAG 2017 – ID 19852 project – P.I. Voliani Valerio. (1) Cassano, D., Pocoví-Martínez, S., and Voliani, V. (2018) Ultrasmall-in-Nano Approach: Enabling the Translation of Metal Nanomaterials to Clinics. Bioconjug. Chem. 29, 4–16. (2) Vlamidis, Y., and Voliani, V. (2018) Bringing Again Noble Metal Nanoparticles to the Forefront of Cancer Therapy. Front. Bioeng. Biotechnol. 6, 143. (3) Cassano, D., Rota Martir, D., Signore, G., Piazza, V., and Voliani, V. (2015) Biodegradable hollow silica nanospheres containing gold nanoparticle arrays. Chem. Commun. 51, 9939–9941. (4) Cassano, D., David, J., Luin, S., and Voliani, V. (2017) Passion fruit-like nano-architectures: a general synthesis route. Sci. Rep. 7, 43795. (5) Armanetti, P., Pocoví-Martínez, S., Flori, A., Avigo, C., Cassano, D., Menichetti, L., and Voliani, V. (2018) Dual photoacoustic/ultrasound multi-parametric imaging from passion fruit-like nano-architectures. Nanomedicine Nanotechnology, Biol. Med. 14, 1787–1795. (6) Cassano, D., Santi, M., Cappello, V., Luin, S., Signore, G., and Voliani, V. (2016) Biodegradable Passion Fruit-Like Nano-Architectures as Carriers for Cisplatin Prodrug. Part. Part. Syst. Charact. 33, 818–824. (7) Mapanao, A. K., Santi, M., Faraci, P., Cappello, V., Cassano, D., and Voliani, V. (2018) Endogenously Triggerable Ultrasmall-in-Nano Architectures: Targeting Assessment on 3D Pancreatic Carcinoma Spheroids. ACS Omega 3, 11796–11801. (8) Cassano, D., Santi, M., D’Autilia, F., Mapanao, A. K., Luin, S., and Voliani, V. (2019) Photothermal effect by NIR-responsive excretable ultrasmall-in-nano architectures. Mater. Horizons 6, 531–537.

Resume : The nanoparticles are due to their unique physico-chemical properties and large surface/volume ratio highly beneficial in a diverse technological application such as plasmonics, energy harvesting, biomedical applications or (bio)sensing. Although different strategies were successfully used for the production of nanoparticles, gas-phase synthesis based on so-called gas aggregation sources (GAS) of nanoparticles gains increasing attention. The main advantage of this high-tech, vacuum-based technique is that it allows for the production of high purity nanoparticles with well-defined structure and size distribution. The use of GAS enables also the deposition of spatially homogeneous nanoparticle arrays with the well-controlled amount of deposited nanoparticles. Last, but not least, the gas aggregation sources of nanoparticles can be easily combined with other vacuum-based deposition procedures (e.g. plasma enhanced chemical vapor deposition, magnetron sputtering) that makes it possible to produce more complex functional nanomaterials needed in various technological fields. In this contribution, three examples of the possible use of gas aggregation sources will be discussed: (i) synthesis of novel antibacterial organic/inorganic nanocomposite coatings and (ii) fabrication of nanostructured coatings with tailor-made wettability (iii) application of gas-phase synthetized metallic nanoparticles for the Laser Desorption Ionization Mass Spectrometry.

Resume : Nowadays, the most promising approach towards cancer therapy is merging different modalities resulting in higher efficiency in the eradication of cancer cells. In this area, a lot of attention has been drawn by polydopamine which has been recognized as an extraordinarily active and biocompatible photothermal agent. This polymer has just recently entered the field of material chemistry, nanotechnology and biomedicine. In this talk, the merging of polydopamine with magnetic nanoparticles and polymeric nanoparticles-PAMAM dendrimers and their application in combined chemo- and photothermal therapy of liver cancer will be presented. To the most aggressive and lethal types of cancer of the central nervous system belongs to glioblastoma. Importantly, brain tumour cells overexpress several proteins that play a crucial role in tumorigenesis and may be exploited as therapeutic targets. One of such target can be an extracellular matrix glycoprotein - tenascin-C (TN-C). A down-regulation of TN-C by RNA interference (RNAi) is a very promising strategy in cancer therapy. Thus, the second part of the lecture will be about the application of magnetic nanoparticles and polydopamine nanoparticles in gene and combined gene and photothermal therapy of glioblastoma. The research was financed by The National Science Centre, Poland under project number 2016/21/B/ST8/00477 and by the National Center for Research and Development under research programme LIDER/11/0055/L-7/15/NCBiR/2016.

Resume : There has been an extensive development in the area of nanotechnology mediated drug delivery in the recent years for the treatment of cancer because of their selective approach. Amalgamation of two drugs exhibits synergistic effects as reported in many literatures. Additionally, the efficiency of chemotherapeutics increases when used along with thermo or radiotherapy. In this direction, we synthesised a multifunctional mesoporous dual drug loaded Fe3O4 magnetic nanoparticles by solvothermal method. Fe3O4 nanoparticles shows a well distributed spherical morphology having diameter ~24.9 nm and crystallite size of around 15.6 nm (Fig.1a). The structure is mesoporous with specific surface area of 63.5 m²/g suitable for higher quantity of drug loading. Anticancerous drug DOX is getting trapped onto the pores of the nanoparticles and having loading capacity of ~88.5%. The system shows slow and sustained release in both pH 5 and 7.4 in a biomimicking environment probably because of thin layer of polymer coating. The bare nanoparticles show little toxicity towards L929 and MDA-MB-231 cells probably because of reactive oxygen species (ROS) generation. ROS generation study was performed by using H2DCFDA and it shows the formation of ROS when the cells were incubated with 1000 µg/ml along with 300 µM H2O2 (Fig.1b). Another drug Tannic acid, a polyphenolic drug has been loaded onto the NPs by a novel Layer by Layer (LBL) technique. Tannic acid forms hydrogen bond with the PEG in which TA acts as a hydrogen donor and PEG act as hydrogen acceptor and shows a decent loading capacity onto the nanoparticles. The % cell viability of MDA-MB-231 cells was ~50.75 % which reduced to ~36.16% when treated with dual drug loaded nanoparticle (conc.1000 µg/ml). In tumor tissue the expression of p53 is enhanced by DOX results in tumor growth inhibition. Further tannic acid activate p53, thus amalgamation of TA and DOX causes irreparable DNA damage. The nanoparticle at a concentration of 1 mg/ml reaches hyperthermic temperature within ~120 seconds at the applied frequency of 316 KHz and AC magnetic field strength of 35.2kA/m. Hence, the mesoporous Fe3O4 nanoparticles can be efficiently utilized for thermochemotherapy of cancer as well as to combat the drug resistance of tumor.

Resume : The use of medical devices has grown significantly over the last decades, and has become a major part of modern medicine and our daily life. Infection of implanted medical devices (biomaterials), like catheters, prosthetic heart valves or orthopedic implants, can have disastrous consequences, including removal of the device. For still not well understood reasons, the presence of a foreign body strongly increases susceptibility to infection. These so-called biomaterial-associated infections (BAI) are mainly caused by Staphylococcus aureus and Staphylococcus epidermidis. The presentation will focus on the development and characterization of novel antimicrobial agents and delivery systems, and their effectiveness in the prevention of BAI and other difficult-to-treat biofilm infections.

Resume : Implant surgery is often accompanied by a bacterial infection related to biofilm formation on their surfaces. Already grown biofilm is very difficult to treat because such bacteria are more resistant against most of the antibiotics. An alternative way is to cover the implant by the smart antibacterial film. Besides the antibiotics, the antibacterial metals can be used as an antibacterial agent. The nanocomposites consisted of Cu nanoparticles fixed in water-permeable plasma polymer matrix acting as a diffusion barrier can offer a large metallic surface for ion production, while maintaining the negligible amount of metal in the patient body. The sandwich nanostructures were fabricated by the sequential deposition of plasma polymer and nanoparticles prepared by means of gas aggregation nanoparticle source. The vacuum-based beam deposition of nanoparticles allowed (i) their high purity grade fabrication and (ii) their homogeneous deposition over a large area. The huge advantage of nitrogen-rich plasma polymers is their ability to immobilize antibiotics (ampicillin and ciprofloxacin). Antibiotics loading is strongly connected to film chemical composition, meanwhile, their release can be controlled by an additional diffusion barrier. The problem of bacteria getting resistant by long-term antibiotics dosing can be elegantly solved by multistage antibacterial action of quicky released antibiotics accompanied with long-term metallic ion release. Supported by GACR 19-20168S

Resume : Gold nanosponges, or nanoporous gold nanoparticles, possess a percolated nanoporous structure over the entire nanoparticles. The optical and plasmonic properties of gold nanosponges and its related hybrid nanosponges are very fascinating due to the unique structural feature, and are controllable and tuneable in a large scope by changing the structural parameters like pore/ligament size, porosity, particle size, particles form, and hybrid structure. The nanosponges show the strong polarization dependence and multiple resonances behavior. They exhibit high density of hot-spots with significantly higher local field enhancement. Strong nonlinear optical properties are confirmed by their high-order photoemission behavior, whereby long-lived plasmon modes are also clearly observed. All this is very important and relevant for the applications in enhanced Raman scattering, fluorescence manipulation, sensing, and nonlinear photonics.

Resume : There is great promise for new scientific and technical breakthroughs, specifically around biomaterials, to address global health challenges. New biomaterials can serve as replacement body parts, reduce healing time, and reduce reliance on anti- biotics and the rise of ?superbugs.? Biomaterials can be incorporated into sensors that can improve quality of life for those suffering from noncommunicable diseases such as seizures and diabetes as well as detect infections on medical implants. Creating new breakthroughs in biomaterials that make it from ?bench to bedside? requires novel innovation ecosystems. Nanomaterials, in particular, have led this revolution. In the introduction, we discuss the current views and challenges in ?translational nano medicine? as a framework for creating innovation ecosystems and to bring biomaterials from bench to bedside. We highlight many different key areas of nanobiomaterials applications. We then describe how biomaterials should be developed within the translational nanomedicine framework, receiving regulatory approval for such implants.

Resume : 14 years ago, we pioneers a one-of-a-kind open access journal to emphasize the growing world-wide interest in nanomedicine: The International Journal of Nanomedicine by Dove Medical Press (which is now part of the Taylor and Francis Publishing group) and is a member of the Committee on Publication Ethics (COPE) endorsing the International Committee of Medical Journal Editors (ICMJE) Recommendations for the Conduct, Reporting, Editing and Publication of Scholarly Work in Medical Journals as well as the GPP3 guidelines regarding authorship. Since that time, interest in nanotechnology across all of medicine has grown exponentially. This talk will focus on research for the design, synthesis, and evaluation of nanomaterials for various medical applications. This includes self-assembled chemistries, nanoparticles, nanotubes, and nanostructured surfaces. Medical applications include inhibiting bacteria growth, inflammation, and promoting tissue growth. Tissues of particular interest are bone, cartilage, skin, nervous system, bladder, cardiovascular, and vascular. There is also an interest in anti-cancer applications where nanomaterials can be used to decrease cancer cell functions without the use of pharmaceutical agents. There is also a large interest in developing in situ sensors which can sense biological responses to medical devices and respond in real time to ensure implant success. Lastly, there is an interest in understanding the environmental and human health toxicity of nanomaterials. This talk will summarize the more prominent advances in nanomedicine and look forward to the next 14 years of the International Journal of Nanomedicine.

Resume : Bone regeneration is a complex physiological process with the growing need for new solutions in tissue engineering.[1] One of the most promising approaches uses electrospun fiber scaffolds which provide structural support similar to the native bone extracellular matrix (ECM) giving the cells a familiar environment for tissue growth.[2] Electrospinning is a scalable and versatile method that allows tailoring of the physicochemical properties and geometry of obtained fiber meshes.[3] Properties tailoring is made possible thanks to many tunable variables such as voltage and it’s polarity, solvents and their ratios, distance from the collector, ambient humidity, temperature and flow rate of used solution.[4] With voltage polarity being a crucial factor influencing surface charge of obtained fibers.[5] As the bone was reported to be piezoelectric, in this research we focused on Poly(vinylidene fluoride) (PVDF) as extracellular matrix replacement. PVDF is well known biocompatible, semi-crystalline polymer. PVDF exhibits piezoelectric properties due to its crystalline all-trans(TTTT) β-phase making it a perfect candidate for bioengineering bone scaffolds. In this research, the influence of voltage polarity on the surface charge of PVDF fibers and their interaction with cells was verified. [6] The osteoblast-like cells attachment, proliferation, and growth were investigated using scanning electron microscopy (SEM), Focused Ion Beam Scanning Electron Microscopy (FIB-SEM) and Fluorescence microscopy. Surface chemistry and potential were investigated using X-ray photoelectron spectroscopy (XPS) and Kalvin probe force microscopy (KPFM) respectively. We verified that the surface charge of PVDF can be controlled with voltage polarity during electrospinning. Moreover, enhanced cell proliferation and mineralization were observed when negative voltage polarity was used showing great potential in bone regeneration processes. References [1] V. Thomas, D. R. Dean, Y. K. Vohra, Curr. Nanosci. 2006, 2, 155. [2] S. Metwally, J. E. Karbowniczek, P. K. Szewczyk, M. M. Marzec, A. Bernasik, U. Stachewicz, Adv. Mater. Interfaces 2018, 1801211, 1801211. [3] P. K. Szewczyk, D. P. Ura, S. Metwally, J. Knapczyk-Korczak, M. Gajek, M. M. Marzec, A. Bernasik, U. Stachewicz, Polymers (Basel). 2019, 11, 34. [4] K. Garg, G. L. Bowlin, Biomicrofluidics 2011, 5. [5] U. Stachewicz, C. A. Stone, C. R. Willis, A. H. Barber, J. Mater. Chem. 2012, 22, 22935. [6] P. K. Szewczyk, S. Metwally, J. E. Karbowniczek, M. M. Marzec, E. Stodolak-Zych, A. Gruszczyński, A. Bernasik, U. Stachewicz, ACS Biomater. Sci. Eng. 2019, 5, 582.

Resume : The aim of the study was to obtain a polylactide spongy bone implant to be a carrier of platelet rich plasma (PRP). Polylactide (PLA) demonstrated osteoconductive properties in many clinical trials, however insufficient in the case of larger defects healing. PLA need to be provided together with bone growth factors included for example in PRP. Deposition of calcium phosphate salts was applied both to increase the absorbability of hydrophobic PLA with PRP and to facilitate the osteoinductive properties of the implant. PLA implants were obtained by the freeze-extraction method, then were modified through a biomimetic deposition of calcium phosphate salts. The efficiency of the mineralization process was increased. Implant surface was characterized by SEM, FTIR and EDS analysis. Mass absorbability and open porosity of implants were measured by the hydrostatic weighing method. Obtained implants were soaked with animal plasma through static soaking and centrifugation. The presence of plasma inside the implant was determined by EDS, FTIR and elementary analysis. Influence of centrifugation with plasma on the internal morphology was determined by SEM. Implants with open porosity above 80% and volume of about 10 cm3 were obtained. Mass absorbability with isopropanol was up to 1400%. Mineralization process enabled the plasma to enter the internal structure of PLA implant. Mass absorbability with plasma was in a range of 350-1700% depending on the soaking mode and mineralization type.

Resume : Limbal epithelial stem cell culture has reached the point of development that allows its adequate use in tissue engineering. However, the survival of the cells after transplantation in host tissue has not been successful. We have designed and produced a microfeature poly (glycerol sebacate) methacrylate (PGS-M) implantable scaffolds with well-defined niches whose 3D shape can be modified as required. These stem cell pockets are expected to improve corneal healing, increasing cell survival, and efficiently deliver limbal stem cells. PGS-M synthesis was carried out by polycondensation of sebacic acid and glycerol. Methacrylate groups were added to the PGS molecule to allow UV curing and creation of accurate morphologies. Two variants PGS-M scaffolds were synthesized: PGS-M high internal phase emulsions (HIPEs) and transparent PGS-M scaffolds. The chemical characterization was carried out through FTIR-ATR, NMR, GPC, TGA, DSC analysis which confirmed the addition of methacrylate groups in PGS molecule. The mechanical testing and degradation studies were also carried out according with the ISO 30:2017 standard. The scaffold morphology was visualized using SEM and confocal light microscopy. The biocompatibility of the scaffolds was analysed using Resazurin, Picogreen and LDH test. This polymer shows high biocompatibility, tuneable degradation, mechanical and physical surface properties, making it an ideal candidate for soft-tissue applications. In vitro testing suggests that microfeature PSG-M-based scaffolds are a promising alternative for the development of new scaffolds for corneal regeneration. Future work will focus on a new generation of more complex PGS-M models which mimic the curvature of the native cornea.

Resume : Progress in the field of nanoparticles resulted in rapid development of multiple products and technologies intended for biomedical applications. However, some nanoparticle formulations may bear both a threat to the environment and human health. We start to realize the challenges and opportunities that lie ahead in the biomedical applications of nanoparticles. Here, we summarize current state-of-the-art on modulation of cellular activity by nanoparticles. We demonstrate the complexity of cellular responses to functionalized nanoparticles and underline challenges lying in the identification of molecular mechanisms affected by nanoparticles. From one hand we show, that prolonged exposure of the macrophages to nanoparticles leads to a significantly enhanced production of reactive oxygen species associated with a long-lasting activation of JNK kinases and induction of apoptosis. From another hand, one can use external pulsed magnetic fields for efficient cell labelling with magnetic nanoparticles. Furthermore, we decoupled molecular mechanisms of nanoparticles action on cancer cells and used specifically functionalized nanoparticles as anti-cancer drugs that can bypass a tumor cell’s ability to develop drug resistance. We propose an idea that subcytotoxic doses of nanoparticles could be relevant for induction of subcellular structural changes with possible involvement of mTORC1 signaling. Deciphering molecular mechanisms of nanoparticle-mediated mTOR modulation will provide fundamental knowledge which could help in developing safe and efficient nano-therapeutics.

Resume : The fabrication of water-repellent surfaces is a well-known category of bio-inspired materials. Studying the microstructure and composition of water repellent surfaces found in nature reveals that a highly rough surface morphology and a hydrophobic coating are keys to their functionality. Developing surface roughness can range from simplistic spray coating methods, to the use of moulds to produce oriented nano/micro-structures. Aerosol-assisted Chemical vapour deposition (AACVD) has been reported for the deposition of thermosetting polymers resulting in highly rough water-repellent coatings. This method relies on the generation of an aerosol from a polymer solution, which would be heated to evaporate the solvent and cure the polymer, and then impact a substrate to create a built-up microstructures assembled from the cured polymer droplets. Although AACVD has been used to develop novel water repellent surfaces, the techniques wider applicability is currently limited. The research to be presented is a further development of AACVD -thermally activated AACVD (ta-AACVD)-, which is focused on providing wider applicability. In the ta-AACVD method, the substrates are kept outside of the CVD reactor, and so the deposition occurs at room temperature. This allows for deposition on temperature sensitive substrates. The ta-AACVD method not only demonstrates applicability to water-repellent coatings, but also is highly relevant to coatings manufacture or thin film deposition approaches.

Resume : A promising material that possesses bactericidal properties is a composite material based on Titanium (IV) oxide. This is due to its high chemical resistance and the ability to implement a number of physical and chemical processes with the formation of non-toxic products. Actuality is the creation of modified materials by introducing into their structure other elements - metals or metals, the so-called doping - the introduction of impurity atoms at the position of Oxygen in the structure of TiO2. Cation doping is carried out by the introduction of metal cations into the crystalline structure of Titanium (IV) oxide at the position of Ti4 ions. Cations of rare-earth (Y, Ce, Pr, Nd, Yb), noble (Au, Ag, Pt) and transition metals (Zn, Cd, Zr, V, Ni, Cr, Mo, W, Fe, Co, Cu) can be used. ) Dipping with cations expands the absorption spectrum of TiO2 and increases the oxidative-reducing potential of the formed radicals. The nature and concentration of additives change the distribution of charge on the surface of TiO2, affects photocatalytic activity. However, the disadvantages of doping in position Ti4 is an increased degree of recombination of charges, which leads to a decrease in photocatalytic activity of TiO2 even under the influence of UV light. Modern studies confirm that the use of anionic additives rather than cationic ones is more effective. Samples of TiO2, doped with nonmetallic elements (Carbon, Sulfur, Fluor, Nitrogen) in the anionic positions of Oxygen are characterized by high photocatalytic activity in the visible and UV regions of the solar spectrum. The paper is devoted to rewiew of the improvement of the conditions for the synthesis of Titanium (IV) sulphur oxide oxide, to study the dependence of antibacterial properties on the sulfur concentration and temperature processing of samples in relation to bacteria Bacillus subtilis. The results of the research show that the nano-dispersed Titanium (IV) oxide doped by Sulfur possesses antibacterial properties relative to the Bacillus subtilis bacterium compared to the undoped TiO2 rutile modification. The largest area of the growth retardation zone is shown in samples from 0.01 to 1% by weight. Sulfur and roasted at a temperature of 300-500 ºС. The phase composition of the samples was investigated by X-ray diffraction analysis. It was found that S-TiO2 samples obtained by the proposed method, sulfur, are most likely not introduced into its crystalline lattice, but is contained in the crystallites of thiourea adsorbed on TiO2 surface. Given the tangible effect of antibacterial action, highly dispersed Titanium (IV) oxide, doped by Sulfur, can be recommended for the production of food packaging.

Resume : In the framework of the current global healthcare system, a particular attention is paid to the patients suffering from certain sicknesses. Unfortunately, medical treatment is not always successful and our society is continuously loosing thousands and millions of lives from cardiovascular, oncological, viral, bacterial and other severe diseases. In this context, there is an urgent need to shift the paradigm in healthcare in order to focus on early diagnostics and prevention of diseases. This challenge can be addressed efficiently via the development of smart personalized electronics for continuous multiparametric monitoring of our health condition combined with an appropriate analytical platform identifying any deviations and making a correct prognosis. Non-invasive permanent monitoring of a person’s health condition can be realized via a continuous analysis of sweat and exhaled air since they contain specific molecular “markers” associated with the appearance of certain diseases. While a tremendous progress was achieved for sensing in liquids, the problem of selective recognition of the target components in a gas phase still remains largely unsolved. This lecture will summarize the most recent results of our research focused on the development of highly sensitive and selective gas sensors using field effect transistors and resistors in combination with organic and hybrid semiconductors, e.g. based on complex metal halides with perovskite crystal structure.