Bioinspired and biointegrated materials as new frontiers nanomaterials

Resume : Countless efforts are made by scientist to design different type of nanostructures, in the investigation for next generation cancer care applications. Various nanostructures often employ multimodality and show encouraging results at preclinical stage in cancer therapy. Specially designed smart nanostructures such as hybrid nanostructures are responsive to external physical stimuli such as light, magnetic field, electric, ultrasound, radio frequency, X-ray, etc are currently being investigated for cancer therapy. Thus, hybrid nanostructures provide a unique combination of important properties to address key challenges in modern cancer therapy: (i) an active tumor targeting mechanism of therapeutic drugs driven by a physical force rather than passive antibody matching, (ii) an externally/remotely controlled drugs on-demand release mechanism, and (iii) a capability for advanced image guided tumor therapy and therapy monitoring. The present report/talk cover various type of nanostructures that are developed by our group and those are responsive to magnetic and light-triggered modalities currently being developed for nonconventional cancer treatments. The physical basis of nanostructures and stimuli responsive modality is explained; so audience with a physics or, materials science background can easily grasp new developments in this field.

Resume : Magnetic-plasmonic, Fe3O4-Au nanoparticles have been of interest in recent years, owing to their bifunctionality and biocompatibility. A plasmonic gold shell facilitates enhanced optical properties, with strong light scattering and absorption capabilities, facilitating bioimaging, surface-enhanced Raman and photothermal activity. Furthermore, thanks to its magnetic core, magnetic manipulation can be achieved which can be exploited in magnetic-field directed drug delivery, MRI contrast imaging and alternating magnetic-field hyperthermia. With great potential for clinical translation, it is important to uncover the physical properties these particles possess, which may help to optimise the stimuli applied to achieve the most efficient theranostics. Herein, superparamagnetic cores are functionalised with varying stages of gold growth from core-satellite structure to full gold shell growth. The optical extinction and single-particle scattering spectra of the various nanostructures are collected, exposing a spectral drift (up to 110 nm) or difference between the extinction and scattering maxima wavelengths. We explore how such a large drift may be of use in multimodal nanotheranostics, where photothermal therapy is conducted near the maximum absorption wavelength and imaging is carried out near the scattering maximum. COMSOL Multiphysics ® was used to create finite element analysis (FEA) models in wave optics and heat transfer to support the experimental findings. We also explore the effects of the gold shell on the magnetic properties of the multistage nanoparticles. This work was supported by Science Foundation Ireland (SFI) centre CÚRAM, the European Regional Development Fund (Grant Number 13/RC/2073), Marie Sklodowska-Curie Grant Agreement No. 751903. and CDA award 13CDA2221.

Resume : The induction of the heat by the magnetic nanoparticles (especially superparamagnetic iron oxide nanoparticles – i.e., SPIONs (i.e., Fe3O4/Fe2O3)) under the exposure of an alternating magnetic field (AMF) has a remarkable potential for being utilized in distinct non-invasive cancer nanotherapeutics such as magnetic hyperthermia therapy (or thermotherapy) and magnetically-triggered release of drugs for chemotherapy. But, the poor induction efficacies (estimated using parameters such as specific absorption rate (SAR) and/or intrinsic loss power (ILP)) of these SPIONs in the controlled environments have hampered their practical implementation so far. This could be mainly attributed to the significant lack of any of the following properties of the SPIONs: suitable size/shape, uniform aqueous dispersibility, biocompatibility, saturation magnetization and/or surface chemistry (for cell uptake/ functionalization). Therefore, it is highly desirable to prepare the SPIONs with the improved physicochemical, magnetic and biological properties for efficient nanotherapeutics. We have approached this via two different processes. In the first process, we have surface-engineered (individual or combined) (i) the unicore hydrophilic SPIONs via π-π conjugated carboxylic acid (COOH-)/amine (NH2-) based surfactants, and (ii) the multicore hydrophilic SPIONs (also called as iron oxide nanoclusters - IONCs) via ethylene glycol & ethanolamine based solvents in in situ manner through co-precipitation and/or thermolysis synthesis methods. It has been observed that these unicore/multicore SPIONs have possessed better properties including colloidal stability, and showed better efficacies (i.e., heat induction (SAR/ILP) & therapeutic) in the treatment of breast and liver cancers via thermotherapy. In the second process, we have encapsulated the as-synthesized hydrophobic SPIONs inside polymeric nanoparticles along with two diverse drugs – i.e., curcumin (a chemotherapeutic drug) and verapamil/nifedipine (calcium channel blocker (CCB) based drugs) to form multi-functional nanoparticles. The polymeric nanoparticles are made of poly(lactic-co-glycolic acid) (PLGA) in association with different stabilizers (i.e., polyvinyl alcohol (PVA) or d-α-tocopherol polyethylene glycol 1000 succinate (TPGS – vitamin E molecules)). Herein, the in vitro magnetically-triggered drug release studies have revealed that the application of AMF has effectually enhanced the discharge of the drugs, which have consequently improved the growth inhibition rates in the cervical and liver cancer cells via combined thermotherapy and chemotherapy (i.e., multimodal cancer nanotherapeutics).

Resume : Hybrid nanostructures of metal, polymer, chalcogenide, oxide, hydroxide, nitride, and carbonaceous materials are believed to promise a great impact on the next generation of cancer diagnosis and therapy technologies. This chapter focuses on hybrid nanostructures that contain two or more distinct nanoparticles assembled in a functional structure that itself is still of nanoscale dimensions. This type of research aims to build a hybrid nanostructure whose medical effects are superior to those that could be realized from any simple mixture of the individual nanostructures. The unique characteristics of hybrid nanostructures in the nanometer range, such as high surface-area-to-volume ratio or shape/size-dependent optical properties, are drastically different from those of their bulk counterparts and hold pledge in the clinical field for disease therapeutics. This work deals with various kinds of novel hybrid nanostructures such as TiO2@Au, nanotube, silica, gold, and polymer that have demonstrated potential biogenic applications, especially in cancer research, including detection and treatments. Synergistic effects corroborated in these hybrid organic and inorganic nanostructures, useful for theranostics, are also explored in this article.

Resume : Nanoparticle mediated chemotherapy for cancer is a potentially curative treatment modality that has been undergoing rapid technological improvements with the development of nanotechnology. Since chemotherapy is not fully effective at certain therapy resistance tumor cells, a combination of drug and heat can effectively exhibit a tumoricidal effect assuring selective attachment to target sites conserving surrounding healthy tissues. Nanomaterials are potential candidates to get functionalized for both chemotherapy and thermal therapy (hyperthermia) in a single system. Further, the dual drug delivery system using two drugs shows effective synergistic effects which enhances tumor regression capabilities compared to individual analog. In this regard, formulation of nano drug delivery systems by layer-by-layer (LBL) techniques employing dual drug loaded magnetite (Fe3O4) nanoparticles for synergistic chemothermal therapy has been investigated. The multifunctional mesoporous dual drug delivery system having magnetite with spherical morphology and high drug loading capacity shows sustained release in lysosomal and physiological pH. Polyphenolic drug increases the effect of DOX in MDA-MB-231 cells as well as repair the DOX induced cardiotoxicity. Thus this nano drug delivery system can be efficiently utilized for thermo-chemotherapy of cancer as well as to combat the cardiotoxicity induced by DOX which were investigated in vitro in H9C2 cells.

Resume : Breast cancer is the second leading cause of death in women worldwide. The extremely fast development of metastasis and ability to develop resistance mechanism to all the conventional drugs make them very difficult to treat which are the causes of high morbidity and mortality of breast cancer patients. Nanotheranostics can be used for this purpose to implement the integration of diagnostic and therapeutic function in one system using the benefits of nanotechnology, with the purpose to treat cancer like one-size-fits-all scenario. The development of liposomes conjugated to superparamagnetic gold-coated iron oxide nanoparticles (Au-SPIONs) functionalized with an aptamer, to mimic natural antibody targeting, was implemented to allow target delivery of the anticancer drug of doxorubicin (DOX) on triple-negative breast cancer cells. Liposomes with iron oxide nanoparticles (SPIONs) and gold nanoparticles (GNPs) were prepared by ultrasound-assisted and controlled seeded growth synthetic methods, respectively. The aptamers AS1411, ERaptD4 and H2 were loaded by a desolvation cross-linking method and characterized by magnetic and physicochemical techniques. The synthesized nanoparticles were found to be spherical with an average diameter of 90 nm and zeta potential of about -49.4 mV. The level of cell death involved in the pathway of apoptosis, were measured to evaluate the synergistic effect of Au-SPIONs-mediated RF hyperthermia. MCF-7 and MDA-MB-231 human breast cancer cells were treated with different concentrations of Au-SPIONs. After incubation with NPs, the cells were exposed to RF waves (13.56 MHz; 100 W; 15 min). Cellular uptake of nanoparticles was confirmed qualitatively and quantitatively. The in-vitro anti-tumor effect of the designed delivery vehicle on MCF7 and MDA-MB-231 human breast cancer cells was evaluated by cell viability assay. The results obtained from cell viability and apoptosis evaluation showed that NPs and radiofrequency (RF) had no significant effect when applied separately, while their combination had synergistic effects on cell viability percentage and doxorubicin release and the level of apoptosis induction. The experimental results revealed that it could significantly inhibit the proliferation of cancerous cells. Aptamer-functionalized magnetic liposomes improved cellular uptake and efficiency to breast cancer cells as compared to non-targeting nanoparticles because of the high affinity of mentioned aptamer toward the overexpressed nucleolin and targeting of HER2 and ERα on MCF7 and MDA-MB-231 cell surface. The obtained results showed that the use of aptamer-functionalized magneto-plasmonic NPs in the process of hyperthermia and radiofrequency (RF) of cancer holds a great promise to develop a new combinatorial breast cancer therapy strategy.

Resume : Magnetic Hyperthermia Therapy (MHT) with magnetic nanoparticles (MNPs) has emerged as a potential treatment method for cancer either alone or in conjunction with chemo and radiotherapy. The major drawback during such treatment is to control the temperature and distribution of nanoparticles in vivo. In MHT, magnetic nanoparticles when subjected to an alternating current (AC) magnetic field heats the specific region of body or tissue [1]. Heat dissipation by MNPs is measured in terms of specific absorbance rate which in turn depends on magnetic moment, anisotropy energy, density, particle size and size distribution[2]. In the present talk, I will be discussing about synthesis, characterization, surface functionalization of nanocrystalline iron oxide based ferrites for MHT. Iron oxide (magntite) being a class of spinel ferrites due to its proven biocompatibility and good chemical stability is extensively studied and projected for its application in MHT. Other nanoferrites including cobalt ferrite, magnesium ferrite and mixed ferrites like Co-Zn ferrite etc have also been explored for their possible application in MHT [3]. To attain specific absorption rate at lowest particle concentrations, magnetic nanoparticles with uniform size distribution and high magnetic moment need to be synthesized. Tuning of magneto-structural properties will be achieved by choice of proper synthesis route. Once synthesized particle need to be surface functionalized with biocompatible polymers to improve colloidal stability in physiological media and cell compatibility. Finally, magnetic induction heating studies of these surface functionalized nanoferrites can be evaluated in vitro for their potential application as heating mediator in MHT for cancer. References: 1. V. M. Khot, A. B. Salunkhe, N. D. Thorat, R. S. Ningthoujam, and S. H. Pawar, Dalton Trans., 2013, 42, 1249 2. A.B. Salunkhe,, V.M. Khot and S.H. Pawar, Current Topics in Medicinal Chemistry, 2014, 14, 572-594 3. V.M. Khot, A.B. Salunkhe, J.M. Ruso, S.H. Pawar, Journal of Magnetism and Magnetic Materials 384 (2015) 335–343

Resume : High magnetic moment Fe3O4 nanoparticles (NPs) are synthesized through simple co precipitation method by using new generation base Diisopropylamine (DIPA) which plays dual role as reducing agent and surface stabilizer. Spherical NPs with ~ 15 nm size and high magnetization value of about 92 emug-1 at room temperature are obtained by this novel method. High specific absorption rate value of ~717 wg-1is obtained for Fe3O4 NPs in water at an alternating magnetic field of 20kAm-1 and frequency of 267 KHz, which is attributed to high magnetization value. Magneto-polymeric micelle structure is formed by using Pluronic F127, anticancer drug Doxorubicin is conjugated in micelle by covalent linking with ligand molecules for magneto-chemotherapy. Finally, the magnetic resonance imaging (MRI) guided magneto-chemotherapy is achieved on breast cancer (MCF7) cells with ~ 96 % killing of cancer cells.

Resume : A vast variety of biosensors and devices for bio- and molecular electronics calls for ordered arrays of functional bioactive or biological nanoparticles arranged at high density and at predefined positions. One approach to create such arrays on large areas at low cost and under mild conditions is directed self-assembly (DSA), which allows to guide the deposition of entities on chemically or topographically prepatterned surfaces. We use block copolymer (BCP) lithography, a straight-forward upcoming nanolithography technique, to create arrays of guiding patterns for DSA with sub-20 nm sized features such as lines, dots or holes on surfaces of several materials on large areas. In this work, we exemplarily present two approaches to apply nanopatterns created by BCP lithography as templates to guide the arrangement of bionanoparticles into periodically ordered arrays. (i) Ferritin nanoparticles are site-selectively deposited from a colloidal suspension into hexagonally arranged nanopores; (ii) Melanin nanoparticles are site-selectively synthesized employing enzyme-functionalized nanopores as nanobatch reactors. The influence of surface wetting, zeta potentials and deposition/synthesis conditions on the nanoparticle arrangement are investigated by AFM, SEM and analytical TEM.

Resume : Aluminum, with low price and high electric density, is the most abundant metal on earth. Besides, aluminum nanocrystal (AlNC) is expected as an alternative plasmonic material by adjusting its size and shape, leading to the shift of localized surface plasmon resonance (LSPR) band from UV-visible to near-infrared (NIR) regions. Previous research focused on the AlNC-based surface enhanced Raman scattering (SERS) detection throughout the UV region, while recent SERS substrates have been applied in the visible and NIR wavelengths. To facilely control the size and shape of AlNC and thus enhancing the electric field, the chemical synthesis has been reported but restricted to two dimensional (2D) SERS substrate. Therefore, herein, the chemically synthesized AlNC were introduced to develop a novel SERS substrate with low cost and high sensitivity based on inexpensive, lightweight, and disposable quasi-three-dimensional (3D) filter paper. The 3D feature of a filter paper can increase the number of hot spots and analytes in the z-axis direction of the depth of field, thus enhancing the sensitivity. On the other hand, the depth of field of a portable Raman spectrometer is generally larger than that of a microscopic Raman system, due to the simpler optical design. Hence, we believed that a portable Raman spectrometer might become an on-site detection tool to effectively provide higher sensitivity, if accompanying a sensitive 3D SERS substrate. In this work, we successfully synthesized AlNCs in an inert atmosphere based on the decomposition of aluminum precursors. The sizes ranged from 65 to 175 nm by simply controlling the ratio of the cosolvents. In order to prevent AlNCs from oxidation in the solution, a polydopamine (PDA) layer, which thickness was adjustable so as not to affect the electric field intensity, was self-assembled onto the surface of AlNCs. After that, droplets of AlNC@PDA solution and analyte solution were successively dropped onto a ?lter paper with pre-modified a hydrophobic layer. The hydrophobic property can condense the AlNCs and analytes to a small spot on the paper surface after air-drying. All Raman measurements were conducted with a portable 785-nm Raman spectrometer. The SERS signal was strongly enhanced as increasing density of AlNCs on a small contact area of the paper surface, indicating that the significant generation of SERS hot spots between the gaps of the aggregated AlNCs. For example, R6G is exploited as a Raman reporter with a LOD concentration of 10-6 M. More evaluations about the stability, reproducibility and real sample testing are still progressing and the details will be reported during the conference.

Resume : The unique functionalities of polyelectrolyte brushes depend on several types of specific interactions, including solvent structure effects, hydrophobic forces, electrostatic interactions, and specific ion interactions. Subtle variations in the solution environment can lead to conformational and surface structural changes of the polyelectrolyte brushes, which is discussed mainly from a surface interaction perspective in this review. We highlight the use of these surface-grafted polymer films to create functional surfaces for various applications, including non-fouling surfaces, boundary lubricants, as well as stimuli-responsive surfaces. Based on the SFA and AFM methods, the impact factors for constraining the lubricity of polyelectrolyte brushes have been investigated. Experimental results reveal that the charged polymer chains and the osmotic pressure of the counterions can lead to wear resistance and low friction in monovalent salt solution. However, the lubrication can break down in the presence of multivalent counterions, even at very low concentrations, resulting from electrostatic bridging and brush collapse between chains from apposing surfaces and changes in surface topology. This study helps to give some insight into the interchain interactions contained in polyelectrolyte brushes but also can promote their application in many technical, medical, physiological, and biological areas. Additionally, we investigated the structure and antifouling properties of surface tethered zwitterionic peptide monolayers with different peptide chain lengths and charge distributions using a combination of surface plasma resonance (SPR), atomic force microscopy (AFM), and all atomistic molecular dynamics (MD) simulation techniques. Our results demonstrate that longer zwitterionic peptides exhibit better antifouling performance. The patchy charge distributions of the positive and negative charges in the peptides, although affecting the structure of the peptide molecules, do not significantly change the antifouling properties of the peptide monolayers.

Resume : Infectious diseases and the deaths caused due to contact with germ-contaminated surfaces are severe problems worldwide. Antibacterial material based on silver nanowires (AgNWs) has a structural advantage when addressing this issue; this is because agglomeration is minimized when nanowires are fabricated into a film. Therefore, employing AgNWs for antimicrobial applications has garnered continuous interest, and increased research for further improvements has been observed. In this study, an AgNW film was fabricated onto glass by spin-coating and then subjected to surface irradiation up to a dose of 1200 kGy, using a low-energy electron beam (e-beam). This ?e-beam? irradiation changed the surface morphology and chemical composition; consequently, this improved the performance of the film. The generation of a silver (I) oxide (Ag2O) outer layer was identified over the AgNWs by X-ray photoelectron spectroscopy. The antibacterial test corresponding to a contact time of 1-h revealed that the e-beam irradiation increased the antibacterial activity from 93.5 to 97.3 % for Staphylococcus aureus, and from 96.1 to 99.9 % for Escherichia coli. Based on the experimental results and the known antibacterial mechanisms of silver (Ag) nanospecies, we discuss the method by which the antibacterial performance of the AgNW film was improved via the e-beam irradiation. This work provides a simple and swift method to functionally enhance the AgNW antibacterial film via e-beam irradiation.

Resume : Cryopreservation is very important in biotechnological, pharmaceutical, biochemical or food industries as the purpose of storage of protein drugs, cells, tissues and food, and ice slurries for refrigeration systems. Antifreeze protein (AFP) have been received attention with their potential as a cryopreservation agent by their ability to prevent the organisms from freezing at the subzero environment through antifreeze activity such as ice recrystallization inhibition or thermal hysteresis effect. However, it is struggling to apply the natural AFP in practical industries as cryopreservation agent because of their irreversible denaturation and the difficulty in extraction from nature. These challenges have led to developing artificial cryopreservation agents like dimethyl sulfoxide and sodium phosphates but due to the cytotoxicity and less biocompatible of them, the recovery rate of the target matter is too low when they are added. Here, the natural AFP mimetic short peptides conjugated with specific amino acids showing antifreeze activity and fibrous assembly with enhanced ?-? stacking are prepared by supramolecular chemistry to increase both antifreeze activity and biocompatibility. This research might provide a useful strategy to fabricate the cryopreservation agent through the supramolecular nanomaterials and to figure out the mechanism of ice binding to antifreeze protein.

Resume : Directed self-assembly of colloids capable of transducing remotely provided energy into mechanical motion may become instrumental for microfluidics technology and minimally invasive medicine. So far, magnetic torque has been the primary choice for the assembly and actuation of microdevices from ensembles of spherical or anisotropic microparticles. While proof-of-concept examples such as mixers, valves, and swimmers demonstrated the potential of the approach, the functionality of the devices engineered with bottom-up techniques is not comparable to the MEMS devices engineered using conventional top-down manufacturing methods [1, 2]. We developed a methodology that combines rotational motion induced by magnetic torque with contractile linear actuation provided by optomechanical nanogels on the same colloidal system. By combining thermocapillary forces with magnetic manipulation, we realized transient and permanent self-assembly of artificial microrobotic muscle that manifests multiple degrees of freedom actuation. Optomechanical actuation is provided by gold nanorods coated with a thermoresponsive polymer NIPMAM (N-isopropylmethacrylamide). Gold nanorods transduce incident light into surface-localized heat that drives fast (within milliseconds) and powerful polymer collapse (up to 50% strain) due to the transition of the polymer shell from hydrophilic to hydrophobic state above the lower critical solution temperature [3]. We introduced thin films of platinum and nickel around the gold core to augment the heat losses and drive convective flows that bring the particles together, introduce magnetization to the particle, and catalyse reactions that can lead to permanent engagement of particles. Adorning the surface of the particles with a repertoire of functional groups permits programmable self-assembly of complex devices from active and passive components, either through microfluidics or with direct laser writing. The assembly process can be re-initiated in the presence of free particles for sequential assembly and directed self-healing of defects. The presented methodology and selected materials are compatible with biological matter, paving the way for versatile and dexterous biomanipulation. References: [1] T. Sawetzki, S. Rahmouni, C. Bechinger, and D.W.M. Marr. PNAS (2008) 105:20141-20145. [2] A. Snezhko and I. S. Aranson. Nature Materials (2011) 10:698-703. [3] Berna Özkale, et al. Lab on a Chip (2019) 19:778-788.

Resume : Tailoring surface properties of materials for biomedical applications is important to avoid clinical complications. Exemplarily, depositing silver as an antibacterial component or immobilizing functional molecules on medical products are established procedures. (Borcherding et al., 2019; Bronze-Uhle et al., 2019; Ratner, 2013). Having in mind that, both performance and economic constraints need to be considered, we present two approaches for the surface modification of metal oxides sputtered-prepared and characterized by X-ray photoelectron spectroscopy (XPS), atomic force microscopy and contact angle measurements. Following the strategy, octadecylphosphonic acid and etidronate will be immobilized according to previous work (Bronze-Uhle et al., 2019), and then after characterization the mono and bi phosphate surfaces will be compared, etidronate is a bisphosphonate commonly used to treat osteoporosis . In the frame of a second strategy, we considered immobilizing an organosilane containing quaternary ammonium, namely Dimethyloctadecyl[3-(trimethoxysilyl)propyl] ammonium chloride (DMOAP), from a methanolic solution on silicon wafers and titanium oxide. We obtained chloride-free hydrophobic film surfaces that were stable upon immersion in saline aqueous medium during one week. XPS investigations revealed an incomplete hydrolysis of compound on the surface.

Resume : Material cues to influence cell proliferation are a fundamental issue in the fields of Biomaterials, Cell Biology, Tissue Engineering and Regenerative Medicine. This report aims to investigate proliferation of single mammal cells on micropatterned material surfaces. To this end, we prepared cell-adhesive circular microislands with 20 areas on the non-fouling background, and systematically examined adhesion and proliferation behaviors of different kinds of single cells (primary stem and non-stem cells, cancer and normal cell lines) on micropatterns. Based on the analysis of experimental data, we found two critical areas about cell proliferation: (1) the critical spreading area of cells from almost no proliferation to confined proliferation, denoted as AP, (2) the critical spreading area of cells from confined proliferation to almost free proliferation, denoted as AFP. We further summarized the relative size relationship between these two critical areas and the characteristic areas about cell adhesion both on patterned and non-patterned surfaces. While proliferation of single primary cells was affected by cell spreading, those cell lines, irrespective of normal and cancer cells, did not exhibit significant cell spreading effects. As a result, this study reveals that proliferation of single cells is dependent upon spreading area, in particular for primary cells on material surfaces.

Resume : Ge has higher carrier mobility than conventional mainstream material Si, and also has a low crystallization temperature (< 500 °Ｃ), which can be synthesized onto insulators under the heatproof temperature. Therefore, Ge on insulator technology has been widely studied for lowering the fabrication cost and improving the device performance. In particular, Ge-based devices fabricated on flexible plastic substrates will open up the possibility for developing advanced wearable devices such as multi-functional display. Solid phase crystallization (SPC) is a simple method to directly form polycrystalline Ge (poly-Ge) thin films on insulating substrates at low temperatures. Recently, we found that the control of the atomic density of an amorphous Ge precursor for SPC dramatically enlarged the grain size and updated the highest record of hole mobility of semiconductor thin film on insulator [1,2]. In this study, we applied this method onto plastic substrate. As a result, the SPC-Ge on a plastic substrate exhibited higher hole mobility than that of bulk Si. This result mean that single-crystal wafers are no longer necessary for fabricating a high-mobility semiconductor thin film. Besides, the resulting hole mobility 680 cm2/Vs is the highest value to date among those of semiconductor layers directly formed on insulators at low temperatures. This achievement will give a way to realize advanced electronic and optical devices simultaneously allowing for high performance, inexpensiveness, and flexibility. [1] K. Toko et al., Sci. Rep. 7, 16981 (2017). [2] T. Imajo et al., Applied Physics Express 12, 015508 (2019).

Resume : During the decades, widespread advances have been achieved on nanochannels correspondingly, including nanochannel based DNA sequencing, single-molecular detections, smart sensors, energy transfer/storage and so on. However, researchers focus all interests on the contribution from the functional elements (FEs) at the inner wall (IW) of nanochannels, little attention has been paid on the contribution from the FEs at the outer surface (OS) of nanochannels. Herein, we achieve explicit partition of FEOS and FEIW based on accurate regional-modification of OS and IW. Furthermore, the FEIW are served for ionic gating, and the chosen FEOS (hydrophobic or charged) are served for blocking interference molecules into the nanochannels, decreasing the false signals for the ionic gating in complex environments. Furthermore, we also define a composite factor, areas of a radar map, to evaluate the FEOS performance for blocking interference molecules.

Resume : This study reports the ratiometric photoluminescent detection and quantification of the toxicologically potent organophosphate ester nerve agents paraoxon (PX) and parathion (PT) using red-photoluminescent silicon-based quantum dots (SiQDs) and the green fluorescent protein mAmetrine1.2 (mAm).1 The nerve agents selectively quench SiQD photoluminescence via a dynamic quenching mechanism mediated by organophosphate nitroaromatic groups. The method reported herein afforded micromolar detection limits for PX and PT and is unaffected by inorganic and organic interferents. In addition, paper-based sensors prepared from SiQDs and mAm have been successfully employed for the detection of PX and PT at low concentrations using a color analysis smartphone application. The sensor reported herein can potentially be used in the determination of PX and PT in actual samples. Reference: 1. Robidillo, C. J. T.; Wandelt, S.; Dalangin, R..; Zhang, L.; Yu, H.; Meldrum A.; Campbell, R.E.; Veinot, J. G. C. ACS Appl. Mater. Interfaces 2019, 11, 33478-33488.

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 : Porphyrinoid compounds have been incorporated into bio-based formulations as a strategy to develop photosensitive biomaterials suitable to be used in anti-infective strategies such as the photodynamic antimicrobial therapy. In this work, owing to develop a photosensitive carrier with biodegradable and biocompatible properties, potato starch films doped with porphyrins were developed. The influence of porphyrin’s dosage on the optical, photophysical, physicochemical, mechanical, and biological properties of the obtained starch films was evaluated. Porphyrins gave rise to transparent starch films changing from yellowish to reddish, depending on their native chemical structure. They also changed the films’ water tolerance and mechanical performance. Moreover, due to their ability of generating reactive oxygen species, the developed starch/porphyrin-based films inhibit the Gram-negative Escherichia coli bacterium growth. Therefore, the incorporation of porphyrins into starch-based formulations reveals to be a suitable strategy to develop newly photosensitive biomaterials with improved mechanical and water sensitivity performance. Acknowledgments: Thanks are due to the University of Aveiro and FCT/MCTES for the financial support of QOPNA research Unit (FCT Ref. UID/QUI/00062/2019) and of CICECO-Aveiro Institute of Materials (FCT Ref. UIDB/50011/2020 & UIDP/50011/2020). The authors acknowledge to POTATOPLASTIC project (POCI-01-0247-FEDER- 017938), financed by FEDER through POCI, “Isolago – Indústria de Plásticos, S. A.”, the project leader, and to “A Saloinha, Lda.” for providing potato byproducts. Nuno M. M. Moura thanks his research contract (CDL-CTTRI-88-89-97-ARH/2018) which is funded by national funds (OE), through FCT – Fundação para a Ciência e a Tecnologia, I.P., in the scope of the framework contract foreseen in numbers 4, 5 and 6 of the article 23, of the Law Decree 57/2016, of August 29, changed by Law 57/2017, of July 19.. FCT is also thanked for the Investigator FCT program (Paula Ferreira, IF/00300/2015), for the Individual Call to Scientific Employment Stimulus (Idalina Gonçalves, CEECIND/00430/2017).

Resume : In the field of tissue engineering, a promising approach to obtain a bioactive, biomimetic, and antibiotic implant is the functionalization of a “classical” biocompatible material, for example, titanium, with appropriate biomolecules. For this purpose, we propose preparing self-assembling films of multiple components, allowing the mixing of different biofunctionalities “on demand”. In this context, the immobilization of Extracellular matrix proteins (ECM), such as fibronectin and vitronectin, that are known to promote osteoblasts adhesion, and therefore bone growth, is an interesting strategy in order to improve the osseointegration of titanium. Actually, the immobilization of an entire protein on a surface can present several drawbacks (protein denaturation and loss in the bioactivity), whereas the immobilization of short biomimetic peptides, reproducing the receptor binding site of the protein offers a convenient alternative route. Since osteoblast adhesion can take place by either interaction with RGD motif via cell membrane integrin receptors or interaction between cell membrane heparin sulfate proteoglicans and heparin binding sites on ECM, both RGD sequence (found in ECM proteins such as fibronectin and known to promote adhesion of several cell lines) and the peptide reproducing the 351-359 sequence of human vitronectin HVP (Human Vitronectin Precursor, amino acid sequence FRHRNRKGY), that increases osteoblast adhesion through the second specific mechanism, are expected to enhance osteoblast adhesion to titanium, the most used biomaterial for implants and prosthesis. Chitosan, on the other hand, is a versatile hydrophilic polysaccharide derived from chitin, with a broad antimicrobial spectrum to which Gram-negative and Gram-positive bacteria and fungi are highly susceptible, and is already known in the literature for the ability of its derivatives to firmly graft titanium alloys and show protective effects against some bacterial species, either alone or in combination with other antimicrobial substances such as antibiotics or antimicrobial peptides. In this context, we functionalized titanium surfaces with two different oligopeptides (RGD and HVP) chemically derivatized with chitosan (Chit-RGD and Chit-HVP), as well as, for comparison, with the two peptides alone. The chemical composition, molecular structure, and coverage quality of the obtained biofunctionalized surfaces were investigated by surface-sensitive techniques such as reflection−absorption infrared spectroscopy (RAIRS) and state-of-the-art synchrotron radiation-induced spectroscopies as X-ray photoemission spectroscopy (SR-XPS), and near-edge X-ray absorption fine structure (NEXAFS). Thanks to the so obtained complementary results, we were able to compare the two series of biofunctionalized surfaces, individuating the best candidate for the production of innovative bioactive materials.

Resume : INTRODUCTION Bone tissue can be damaged by aging, some diseases or some accidents. Critical bone injuries and tissue losses have led to the need for the use of various biomaterials in the clinic. Firstly, metals such as cobalt-chromium alloys, stainless steel, titanium alloys have been used in biomedical applications. However, although these biomaterials support bone repair, they are not suitable for the purpose of supporting new bone formation, because they lack biological resorption characteristics. Therefore, many researchers oriented to other alternatives. One of these alternatives is the production of bioceramics such as hydroxyapatite (HA) and tricalcium phosphate. Many studies have shown that bioceramics containing silicon (Si), calcium (Ca) magnesium (Mg) have high bioactivity, biocompatibility, and strong mechanical properties. Therefore, they can be used in bone repair and regeneration as scaffolds with polymers such as polycaprolactone (PCL). The aim of study is to investigate potential of PCL/HA/Akermanite(AKR) and PCL/ carbonated hydroxyapatite (CHA)/AKR fibers produced by electrospinning method for bone tissue engineering. MATERIALS AND METHODS HA was synthesized by microwave irradiation method while CHA was synthesized by nanoemulsion technique. AKR was fabricated vis sol-gel method. After characterizations of bioceramics such as X-Ray Diffraction (XRD) and Fourier Transform Infrared (FT-IR), and bioactivity tests in simulated body fluid (SBF), scaffolds were producing by wet electrospinning. PCL using carrier material and was dissolved in ethanol. After optimization of some parameters such as voltage and flow rate, PCL/HA/AKR and PCL/CHA/AKR fibers were produced. Then, in vitro bioactivity tests of scaffolds were performed in SBF for 1,7 and 14 days to determine apatite layer formation. At the end of the immersion times, scaning electron microscopy (SEM) analysis was used for imaging apatite layers on the fibers. Also, elemental analysis (EDS) was done. Furthermore, cell adhesion, proliferation and osteogenic activity were studied with Saos-2 cells. CONCLUSION HA, CHA and AKR were synthesized respectively by microwave irradiation, nanoemulsion and sol-gel methods. Characterization techniques such as XRD and FT-IR proved that bioceramics produced successfully. In vitro bioactivity experiments showed that there are spherical apatite layer formations on the PCL/HA/AKR and PCL/CHA/AKR fibers produced by wet electrospinning. Moreover, cell proliferation and osteogenic activity of Saos-2 cells on the scaffolds were good.

Resume : Wearable electronic devices represent powerful tools towards long-term health-monitoring due to non-invasive measurement, lightweight and high comfort. To obtain accurate human physical information through the skin surface, the adhesion between the skin surface and devices is pivotal. However, it is still a great challenge for the epidermal electronic devices to achieve conformal attachment to the rough, soft and textured surface of the skin. This challenge is further amplified in hot and humid environments or during exercise, in which the sweat and motion of the human body may cause bonding failure (detachment) of many artificial pressure-sensitive adhesives. Herein we present a facile approach to fabricate a gecko-inspired, natural silk fibroin protein based adhesive for achieving highly conformal, comfortable, adjustable, and biocompatible adhesion on the skin surface. This micro-structured adhesive exhibits reliable and stable bonding force on skin surfaces, even under humid or wet conditions, and can be easily peeled off from the skin without causing significant pain. Such bio-inspired adhesive has a great potential to be applied as functional adhesives for various epidermal electronic sensors in the era of personalized healthcare.

Resume : Nanoparticles mediated drug delivery system has immense therapeutic applications especially in the field of cancer treatment. The chemo-therapeutic efficacy is enhanced when combined with radiation therapy or thermal therapy (Hyperthermia). For thermalchemotherapy, appropriate functionalised magnetic nanoparticles with desired magnetic parameter are pivotal. In this direction, we synthesised a highly aqueous dispersible PEG-dicarboxylic acid functionalised iron oxide (Fe3O4) nanocluster with superior magnetic properties by a simple solvothermal approach. The well distributed nanocluster (size~200nm) are formed by the assembly of smaller nanoparticles. Fe3O4 crystallizes in inverse spinel structure with crystallite size of 16.9 nm and possess mesoporous structure with high specific surface area of 71.3 m²/g. The carboxyl group was activated using hydrazine hydrate to form pH sensitive hydrazone bond which further was utilised to attach with doxorubicin (DOX) through C=O linkage. High drug loading efficacy was achieved due mesoporous nature of the nanoparticles and carboxyl group activation. This system shows higher and sustained release at pH 4.3 in comparison to normal physiological pH of 7.4 because of labile hydrazone bond. The synthesised Fe3O4 nanoclusters are biocompatible upto a concentration of 1mg as observed in vitro in MCF-7 breast cancer cell line. Due to higher saturation magnetisation of the nanocluster, a hyperthermic temperature of ~ 43 ºC was achieved in just 105 s at nanoparticle concentration of 2 mg/ml and at the applied AC magnetic field strength of 35.2 kA/m and frequency of 316 kHz. Hence, the PEGylated mesoporous Fe3O4 nanoclusters can be effectively utilised for thermochemotherapy of cancer.

Resume : The current state of the art in artificial cell science relies on the construction of lipid vesicle membranes whose inherent properties, however, limit their applications particularly in sustaining cell internal biochemistry and communication between neighbors. Polymersomes are considered as ideal alternatives to liposomes because of their enhanced stability, chemical versatility, chemical and mechanical resistance. Nevertheless, the use of polymeric vesicles is restricted due to their low membrane permeability. Here, a suite of porous polymer membranes which is intrinsically permeable to molecules of defined sizes is explored as chassis for artificial cell, with the ideal functionalities of retaining specific molecules (e.g. protein and DNA) but allowing influx and efflux of small molecules (e.g. metabolites, signal molecules and mRNA). The porous vesicles are expected to form directly by self-assembly of copolymers, and the porosity is hypothesized to be controlled by varying experimental parameters during extrusion. The combinations of copolymers involve the mixtures of diblock copolymer PEG-PBD and triblock copolymer PEG-PPO-PEG with different molar ratios, and the solutions of two or more triblock copolymers PEO-PPO-PEO with different head-to-tail ratios. The porous polymer vesicle is novel in artificial cell science; thus, many potential applications can be tapped into, including for spatially-segregated biochemical reactions in polymer-based synthetic organelles.

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

Resume : Endogenous electrical signals regulate plant behaviors towards environmental changes. A deeper understanding of plant electrophysiology sets the foundation for plant-electronic hybridization. Hydrogels are the dominant material used for non-invasive plant electrophysiology measurement. However, conventional gels cannot electrically bridge electrodes with highly textured plants (especially hairy plants) effectively, due to lack of adhesiveness or conformability. Here, we show that surface-active thermogelling polymer can be used to establish an adhesive and conformable ionic interface between hairy plants and electrodes. The thermogelling polymer solution possesses drastic sol-gel transition near ambient temperature, which enables liquid-phase application for conformability to hairy plants. The surface-activity facilitates direct physical interaction between polymer networks and solid surfaces, enhancing interfacial adhesion. Such adhesive thermogel was demonstrated to allow for facile and high-fidelity electrical recording on highly hairy plants. It simplifies electrode setup and promises accessibility to a larger array of plant species, which will promote the development of plant-electronic hybrids towards smart sensing and modulating functions and have wider implications to on-human bioelectronics design.

Resume : The existence of cancer stem cells (CSCs) has been demonstrated in several solid tumors including brain cancer. These CSCs represent a sub-population of cells within tumor bulk that exhibit stem-cell-like characteristics and they are believed to play a significant role in tumor formation and recurrence, metastasis and they are resistant to conventional chemotherapeutic drugs. They are enriched in stem cells markers and markers associated with higher drug resistance and self-renewal. Chemotherapy is a well-accepted treatment modality for different cancer types including glioblastoma, however, its efficacy on glioblastoma still remains far from the best in most cases. The chemotherapeutic drugs are mostly effective on normal cancer cells leaving glioblastoma (GBM) stem-like cells insignificantly affected after treatment. Therefore, the establishment of better treatment strategy is needed in order to combat glioblastoma stem-like cells drug resistance. One such strategy is the induction of differentiation on GBM CSCs to normal cancer cells that will circumvent their self-renewal ability and improve their sensitivity to anti-cancer drugs. Previous literature has used low-intensity ultrasound (LIPUS) to inhibit the proliferation and induce apoptosis in cancer cells. Additionally, we have reported the induction effect of LIPUS on liver CSCs. In the present study, LIPUS was deigned to induce differentiation and concomitantly enhance the sensitivity and an uptake of drug by CSCs isolated from GBM cell line. We first designed and developed three dimensional tumor microenvironment using hyaluronic acid (HA) based polyelectrolyte multilayer (PEM) film system in order facilitate the isolation and enrichment of GBM CSCs. The next step is the use of LIPUS stimulation of GBM CSCs in combination with anti-cancer loaded gold nanoparticles. Colony formation, migration and invasion, putative CSCs marker expression, drug resistance, stem cell related genes expression and immunostaining were all investigated and compared with control group. The results revealed that high colony formation was observed on PEM system after 3 days of culture which continued through 7 days after culture. Higher expression of CD133, higher migration and invasion ability, up-regulation of proteins and genes related to CSCs and an increased drug resistance capacity were observed in cells isolated on PEM film system. From our previous study, LIPUS stimulation may result to down- regulation of CSCs colonies, down-regulation of CSCs related proteins and genes, down-regulation of migration and invasion ability, and an enhanced drug sensitivity of CSCs. Our proposed study design may provide alternative therapeutic strategy on the differentiation and effective combination therapy of glioblastoma CSCs.

Resume : Going beyond the traditional concept of electronic devices, we convey the idea of making electronics edible. This unconventional approach exploits the electronic properties of natural and food-based materials for developing ingestible functional devices. Critical biomedical, pharmaceutical, and food industry applications are targeted by the proposed field. In this framework, we explore the potential of cost-effective and edible substance, honey, to be used as electrolytic gate viscous dielectric. Honey-gated organic field effect transistors (OFETs) based on both n & p type semiconductors are fabricated. A distinctive feature of these transistors is their long-term stability, reproducibility and low voltage < 1V operation in air. Devices exhibit forward-looking electronic performances, notably, electron and hole mobility–capacitance product of 3.5 × 10–3 μF/Vs and 23 × 10–3 μF/Vs, respectively, surpassing ones of the previously reported water-gated OFETs. Furthermore, the observed devices responsivity to humidity provides promising opportunities for sensing applications. We then demonstrate, for the first time, the implementation of honey-based integrated circuits: inverting logic gate and ring oscillator.

Resume : Cervical cancer is the most common malignancy suffered by women worldwide in the female reproductive system. The chemotherapeutic treatment using anticancer drugs are developed recently, but they lack delivery to the targeted tumour tissues. The commonly used anticancer drug paclitaxel is highly efficient against various cancer types, but due to its low solubility the enhancement of its property decreases. Recent advances includes nanotechnology based combinatorial drug delivery systems that offer enhanced pharmacokinetic property due the EPR (enhanced permeable retention), the larger surface area to volume ratio in nanoparticles, it also helps in adsorbing large amount of drug and act as a drug carrier. The combination of nanosystems aids in active or passive drug delivery through the cell membranes via endocytosis. In particular selenium nanoparticles is a well established chemotherapeutic agent due to low toxicity to the normal tissues, when compared to other nanosystems. The selenium nanoparticles act as both prooxidant in the presence of cancer tissues by producing ROS which eventually causes oxidative stress, mitochondrial damage, alter the genetic arrangements of the cancerous tissues, they are also major component of many antioxidant enzymes that also function at protecting from tumour like GSH (glutathione), selenomethioninecystien (recent established amino acid), theoredoxin (Trx) and so on. They act as antioxidant agent for normal tissues by scavenging ROS, regulating the DNA repair proteins, and protecting the damages caused by oxidative stress. In this paper more emphasis is done on the green synthesis of selenium nanoparticles to avoid the utilization of external harmful chemicals. The precursor used for the reduction of the sodium selenite which itself it a harmful chemical which was traditionally used as anticancerous agent, are Mucuna pruriens seed extract which is also a traditional medicine against various cancer types. The extract is used as a bioreductive catalyst which also helps in stabilization of the nanoparticle development. The biosynthesized SeNPs are optimized using BB design for evaluating the optimum particle size and process variable. The optimized SeNPs are then coated with chitosan which acts a biodegradable linker against anticancer drug paclitaxel. The combinatorial nanosystem is evaluated for its anticancerious activity against HeLa cancer cells. This innovative strategy can help in overcoming the drawbacks faced by chemotherapeutic drugs with low solubility, delivery to the targeted sites, highly biodegradable and low toxicity.

Resume : Implantation of biodegradable wafers near the brain surgery site to deliver anti-cancer agents which target residual tumor cells by bypassing the blood-brain barrier has been a promising method for brain tumor treatment. However, further improvement in the prognosis is still necessary. We herein present novel materials and device technologies for drug delivery to brain tumors, i.e., a flexible, sticky, and biodegradable drug-loaded patch integrated with wireless electronics for controlled intracranial drug delivery through mild-thermic actuation. The flexible and bifacially-designed sticky/hydrophobic device allows conformal adhesion on the brain surgery site and provides spatially-controlled and temporarily-extended drug delivery to brain tumors while minimizing unintended drug leakage to the cerebrospinal fluid. Biodegradation of the entire device minimizes potential neurological side-effects. Application of the device to the mouse model confirms tumor volume suppression and improved survival rate. Demonstration in a large animal model (canine model) exhibited its potential for human application.

Resume : Industrial applications of anchorage-dependent cells require large-scale cell culture with multifunctional monitoring of culture conditions and control of cell behaviour. Here, we introduce a large-scale, integrated, and smart cell-culture platform (LISCCP) that facilitates digital mass culture of anchorage-dependent cells. LISCCP is devised through large-scale integration of ultrathin sensors and stimulator arrays in multiple layers. LISCCP provides real-time, 3D, and multimodal monitoring and localized control of the cultured cells, which thereby allows minimizing operation labour and maximizing cell culture performance. Wireless integration of multiple LISCCPs across multiple incubators further amplifies the culture scale and enables digital monitoring and local control of numerous culture layers, making the large-scale culture more efficient. Thus, LISCCP can transform conventional labour-intensive and high-cost cell cultures into efficient digital mass cell cultures. This platform could be useful for industrial applications of cell cultures such as in vitro toxicity testing of drugs and cosmetics and clinical scale production of cells for cell therapy.

Resume : Stimuli-responsive nanostructures have shown great promise for intracellular delivery of anticancer compounds. A critical challenge remains in the exploration of stimuli-responsive nanoparticles for fast drug release. Herein, ROS-responsive nanoparticles were rationally designed to effectively enhance drug release of radiosensitizer agents for synergistic thermo-radiotherapy. In this study, ROS-responsive poly(thiodiethylene malonate) (PSDEM) and PEG-PSDEM-PEG were synthesized and used as the main materials for ROS-responsive PSDEM nanoparticle (MNP) assembly in aqueous conditions. The radiosensitizer, suberoylanilide hydroxamic acid (SAHA), and the photothermal/photodynamic agent, indocyanine green (ICG), were encapsulated in the MNPs via hydrophobic interaction. The encapsulated ICG could generate not only heat but also ROS during NIR laser irradiation. In addition, via the ROS oxidation of the nonpolar sulfide residues in PSDEM into polar sulfoxide residues, the deformation of SAHA/ICG-loaded MNPs (I/S-MNPs) occurred, which this leading the SAHA release. The combination of NIR-triggered radiosensitizing and PTT effect could enhance the following therapeutic efficacy of radiotherapy, as confirmed via in vivo and in vitro evaluations. I/S-MNPs combined with radiotherapy showed the best tumor growth inhibition and the longest surviving time of mice, showing that I/S-MNPs exhibit a high potential for combination with radiotherapy to eliminate the malignant tumor.

Resume : Cancer is a growing public health concern of this century. So far, the major anti-tumor therapeutic approaches, including chemotherapy and radiotheray, still have a lot of limitations in clinical. Besides, it is well acknowledged that the tumor exhibits some mechanisms of immune suppression in the tumor microenvironment (TME) to evade immune surveillance. To overcome these problems, cancer immunotherapy has definitely grabbed the spotlight in recent years. Thereinto, cancer vaccine, especially ?in situ vaccination?, which enhances tumor immunogenicity via local applying of the immunomodulatory adjuvant is a promising option. Cyclic di-guanylate (c-di-GMP), an activator of the stimulator of interferon genes (STING), has been considered as a potential adjuvant in immunotherapy. It could induce the production of type I interferons (IFNs) via the STING-IRF3 pathway in antigen presenting cells (APC), resulting in enhancement of the tumor immunogenicity. However, the efficacy of c-di-GMP is limited by some inherent shortcomings, including the poorly membrane permeance, rapid clearance and the nonspecific distribution in body. So, we attempt to incapsulate the c-di-GMP with positively charged mesoporous silica nanoparticles (MSNs) to overcome its limitaions and induce enhanced antitumor immune response. The PEGylated RITC fluorescent MSNs modified with positively charged molecule (N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride, TA) were synthesized by co-condensation (labeled as RMSN-PEG/TA). The anionic c-di-GMP was loaded into RMSN-PEG/TA via electrostatic interactions (c-di-GMP@RMSN-PEG/TA). The loading amount of c-di-GMP on c-di-GMP@RMSN-PEG/TA was around 3 wt%. RAW264.7 cells treated with c-di-GMP@RMSN-PEG/TA obviously promoted the production of IL-6, IL-1?, and IFN-?, as well as the expression level of phospho-STING (Ser365) protein. The mouse 4T1 breast tumor-bearing Balb/c mice received intratumoral injection of c-di-GMP@RMSN-PEG/TA revealed dramatically tumor growth inhibition compared with the free c-di-GMP treated ones. In addition, the infiltration of activated CD11c+ dendritic cells and CD4+ T cells at the tumor microenvironment were detected by flow cytometry. By utilization of MSNs, we demonstrated that STING agonist c-di-GMP is a quite prospective adjuvant in cancer immunotherapy and MSNs are appropriate vehicles for ?in situ vaccination?.

Resume : Applications in gene or drug delivery call for nanometer precision in the actuation of nanoscopic probes to navigate them reliably towards target tissues and eventually specific cells. While chemical targeting e.g. enables tissue-specific delivery, magnetically propelled nanomotors can navigate through complex biological media[1-2] and can transport material towards individual cells. However, commonly used magnetic materials are not biocompatible (Ni, Co) or possess weak magnetic moments (Fe, Fe3O4). Here, we demonstrate the first actively propelled nanomotors based on a rare-earth free hard magnetic system that is fully biocompatible while exhibiting magnetic moments that rival those of very strong permanent NdFeB micromagnets. We demonstrate cell targeting using gradient-free mT fields. The nanopropellers are fabricated with a physical vapour deposition technique termed glancing angle deposition (GLAD). The results establish biocompatible magnetic micromotors as promising tools for biomedical applications. 1. Wu, Z.; Troll, J.; Jeong, H.-H.; Wei, Q.; Stang, M.; Ziemssen, F.; Wang, Z.; Dong, M.; Schnichels, S.; Qiu, T.; Fischer, P., A swarm of slippery micropropellers penetrates the vitreous body of the eye. Science Advances 2018, 4 (11), eaat4388. 2. Walker, D.; Käsdorf, B. T.; Jeong, H.-H.; Lieleg, O.; Fischer, P., Enzymatically active biomimetic micropropellers for the penetration of mucin gels. Science Advances 2015, 1 (11), e1500501.

Resume : Personalised orthotic devices that provide targeted support to weakened muscles and facilitate treatment of fractured bones, damaged joints or tendons are expected to usher in a new generation of patient-specific solutions without affecting active lifestyle. The latest advances in technologies of Additive Manufacturing allow for fabrication of highly customised designs with finely controlled structure in a fast and cost-efficient process. Utilising state-of-the-art 3D scanning processes, a 3D model of the unique human anatomy is reconstructed through reverse engineering. Subsequently, the bioinspired device design is optimised via Generative Design algorithms, considering the specific needs of each patient, e.g. areas in need of increased ventilation, or wound dressing, towards a thoroughly personalised medical solution. Taking advantage of innovative polymer materials and cutting-edge enhancing additives, smart functionalities, enhanced product strength and durability at lower overall weight are integrated in such devices. This is illustrated in the development of a 3D printed mutlimaterial wrist splint with antimicrobial and tailored mechanical properties using nanocomposite reinforced polymeric materials. By creating this product through Additive Manufacturing, a high level of personalisation is achievable, leading to predefined structures with tunable size and shape, thus allowing for increased breathability, making re-dressing wounds easier and daily tasks untroublesome.

Resume : Nanoparticle (NP) is widely used in biomedical application and cancer treatment due to the minute scale, multi-function, and long retention time. Among the various nanoparticles, the special optical property derived from localized surface plasmon resonance (LSPR) effect of metallic nanoparticles is a major reason that metallic nanoparticles are researched and applied. Copper nanoparticles (CuNPs) exhibit an absorption peak at the wavelength of 590 nm that can transfer the energy of photon to heat and rise the temperature of tumor microenvironment (TME), inducing cell apoptosis, which makes it a possible agent for photothermal therapy. Besides, compared to metals commonly used in cancer therapy such as gold and silver, copper has better biodegradability and is less likely to greatly accumulate in human body.On the other hand, iron nanoparticles (FeNPs), which have the potential to generate reactive oxygen species (ROS) via Fenton or Fenton-like reaction and produce oxygen in excess H2O2, are suitable for cancer treatment. Also, the magnetic property of FeNPs is appropriate for magnetic resonance imaging (MRI) to combine diagnosis and therapy. In drug delivery systems, the efficacy of traditional drugs is usually largely reduced after injection into human body due to their non-specificity, and side effects on normal tissues also emerge. Thus, through modificaiton of drugs on the surface of the FeNPs, when applying an external magnetic field, the nanoparticles could be guided to the targeted area, simultaneously reducing the amount of drugs used and minimizing injuries on normal cells. Also, it has also been proved that an externally applied magnetic field enhances the accumulation of magnetic nanoparticles at tumor sites, which in turn improves the curative efficacy of chemotherapy. Moreover, poly(styrene-co-maleic anhydride) (PSMA) could help increase drug solubility and stability, lengthening the half-life in blood plasma, and it can also improve the pharmacokinetic properties of the drugs. In our previous work, we found that PSMA could also serve as a successful drug carrier loaded with methylene blue (MB) via ?-? stacking and hydrogen bonding, indicating that it is a potential drug delivery platform. In this work, we synthesized dual metal nanoparticles, copper-iron nanoparticles (CuFeNPs), by a simple one-step hydrothermal reduction reaction. The Fe/Cu ratio of product could be controlled by manipulating the Fe/Cu ratio of reactant. The spinel structure of metal core was determined by XRD pattern. Moreover, the ROS generation ability of CuFeNPs was proved to be significantly higher than CuNPs. The magnetic property measured by hysteresis loop gave the potential of MRI agent. The photothermal effect was measured and the temperature was obviously elevated. The result indicated that CuFeNP is a potential agent for MRI and photothermal therapy.

Resume : New adhesives for interaction with human skin are required for multiple applications. These range from wearable electronics to medical devices for diagnostics and therapy. Micropatterned dry adhesives are potential candidate materials allowing for a conformal contact and adhesion based on van der Waals interactions, dismissing the use of glues. At the same time they provide gentle but reliable long-term adhesion, as well as detachment without damaging delicate tissues. In this study, we developed high performance dry adhesives for biomedical purposes. The design consists of an array of elastic microfibrills with an aspect ratio of 3:1, terminated by a viscoelastic top layer of variable thickness. An advanced and robust method was developed to fabricate these film-terminated structures using medical-grade silicone. Systematic investigation of the adhesive properties regarding pull-off stress and work of separation was performed for epoxy substrates of different roughness, ranging from smooth (Rz=0.1 µm) to skin-like roughness (Rz=49.6 µm). The influence of hold time and pre-load for samples with different top layer thickness was evaluated in depth. Enhanced adhesion was observed for the microstructured samples compared to non-structured control samples on surfaces with skin-like roughness. For example, when applying 1.6 kPa compressive pre-stress for 60 seconds on substrates with skin-like roughness, samples with a top layer thickness of 30 µm reached up to approximately 7 kPa pull-off stress. On the contrary, the pull-off stress for the respective flat reference was approximately 1.7 kPa using the same conditions. The improved adhesive properties of the film-terminated adhesion system, particularly on surfaces with skin-like roughness, are attributed to the combined effect of the compliant soft film and the dynamic structural features of the fibrils, indicating the high potential of this adhesion system for skin device applications. Further investigations include a miniaturization of the system, for biomedical applications, e.g. treatment of tympanic membrane perforation. This work on dry adhesives displays a novel design for high performance adhesion systems for wearable electronics and wound dressing applications.

Resume : Biologic scaffolds composed of naturally occurring extracellular matrix (ECM) facilitate the constructive and functional tissue remodeling. Wharton's Jelly (WJ) contains significant amounts of ECM components and it`s a rich source of endogenous growth factors. Herein, we developed gelatin based porous scaffolds supplemented with WJ derived ECM micro-particles and Tannic acid (TA) by freeze-drying technique. TA was incorporated to the gelatin/gelatin-ECM hydrogels for antimicrobial and anti-biofilm purposes against Gram + and Gram- bacteria. Transglutaminase (TGA) was used to crosslink the composite hydrogels and to tailor their mechanical properties. Morphology and dimensions of the resultant scaffolds were characterized by scanning electron microscopy. Scaffolds with different pore sizes were obtained by adjusting the concentration of the gelatin solution. Ideal concentration was defined as 5.6 %v/w which resulted in 54.82 ± 24.6 µm pore diameter and 88.8 % porosity. In vitro cell culture results indicated that the WJ particles loaded porous gelatin scaffold facilitates the attachment and migration of macrophages and mesenchymal stem cells. Wharton?s Jelly derived micro-particles can be a strong candidate as a supplement to tissue engineering scaffolds for improving their functionality and biological activity. Key words: gelatin, Wharton?s jelly, tannic acid, extracellular matrix, scaffold, tissue engineering.

Resume : Functionalized poly(p-xylylenes) can be deposited via chemical vapor deposition (CVD) polymerization to generate ultra thin films as conformal coatings and, due to the pre-defined chemical functionalities, provide a flexible solution to surface engineering challenges as they decouple surface design from bulk properties. Hence, the technology comprises essentially a one-step coating procedure to generate functionalized surfaces without requiring any kind of post-treatment once the films are deposited. The CVD-based polymer films can be generically applied to a wide variety of substrates and establish a reactive interface that allows for further modification. The simplicity in providing a wide range of functional groups, the excellent adhesion to various substrates, and its applicability to devices with three-dimensional geometries are key advantages when compared to polymers deposited by solvent-based methods. Related applications have been shown to provide engineered interface properties to resist bacteria/biofilm formation, to prevent non-specific adsorption of proteins and cells (antifouling), and to manipulate cellular activities including proliferation, differentiation, and spheroids formation for a range of cells and stem cells. Furthermore, the coating technology has used for the encapsulation of liquids and to result in a revolutionary production of a intraocular lens (IOL), and the new IOL ehxibited: (i) enhanced compatibility and stability to avoid leaching of potential harmful substances to the surrounding biological environment and (ii) customizable optical and biological properties for diverse patient needs. Finally, instead of forming conventional thin films, the vapor deposition of the poly-para-xylylene polymers on a dynamic substrate, i.e., sublimating ice, was found to produce three dimensional bulk materials and composites with controllable porosity and size.

Resume : Blindness is one of the most severe problems that degrade the quality of human life, rather than any other disorders. Various methods for restoring the vision have been studied. Among them, electronic prosthetic devices for a visually-impaired person allows the individual to recognize the phase and movement of an object. It is based on the principle of converting an external light signal into an electric signal that is transmitted to the human optic nerve, which allows a person to perceive the electric signal as light. This retinal prosthesis has undergone considerable development over the last few decades; however, there are several challenges to be solved. First, the resolution is too low to visualize the information from the outside to human eye. This problem is mainly originated from the high impedance of the electrodes. Second, the mechanical modulus of the material within the device is a mismatch to the modulus of the retina tissues, followed by severe inflammation and permanent damage to the retina. Finally, since this device is planned to be implanted on the human eye, the reliable operation is important. Here, we presented the high-resolution, flexible retinal prosthesis based on three-dimensional (3D) soft stimulation electrodes for blind people. The high-resolution phototransistor array with a stimulation electrode allows the patient to perceive the image clearly. 3D structure of the electrode reduces the impedance of each pixel so that the single-pixel can be integrated into high density without any electrical breakdown. Since we formed 3D electrodes using soft, self-healable materials, this stimulation electrode hardly damages the retina surface and easily restore their electrical characteristics under various mechanical deformations, suggesting the reliable operation of the implanted retinal prosthesis. Furthermore, in-vitro and in-vivo animal experiments using mouse and rabbit provided enough biocompatibility for the human trial. This optoelectronic retinal prosthesis using high-resolution, flexible transistor arrays provides a substantial chance to step-up for next-generation implantable electronic devices.

Resume : Sequential processes combined with specific lithographic methods allow the fabrication of advanced materials structures. In the present work we have used self-assembled colloidal monolayers as lithographic structures for the conformation of ordered Si submicrometer pillars by reactive ion etching. We have explored different discharge conditions to optimize the Si pillar geometry. Selected structures were further decorated with gold by conventional sputtering, prior to lift-off of the colloidal monolayer. The resulting structures consist of a gold crown, that is, a cylindrical coating on the edge of the Si pillar and a cavity on top. We have analysed the Au structures in terms of electronic properties by using X-ray absorption spectroscopy prior and after post-processing with thermal annealing at 300ºC and/or interaction with a gold etchant solution (KI). The angular dependent analysis of the plasmonic properties has been studied by Fourier transformed UV-vis measurements. Particular conditions have been selected to perform a SERS evaluation of these platforms with two model dyes, prior to confirming the potential interest for the well-resolved analysis of biomolecules of several tens of KDa.

Resume : The use of functionalized nanoparticles (NPs) for pollutant removal applications in a biological environment emerged recently as an important topic. Nowadays, studies have shown the promising capacity of magnetic iron oxide (IO) nanoparticles for removing of pollutants from water or human body. Magnetic nanoparticles can be easily separated from water under an external magnetic field. Moreover, they may have a high surface-area that allow high removal capacity of micro-pollutants with a small quantity1. In that context, we have designed iron oxide nanostructures to improve the phosphate removal during the peritoneal dialysis process. At first, we have developed the synthesis of magnetic raspberry shaped nanostructures (RSN) by modified-polyol solvothermal methods2,3.This IO nanostructures consist in orientated aggregates (150-500 nm) of nanocrystals (10-25 nm) which preserve them from oxidation and provide a very high saturation magnetization (Ms~85 emu/g). In addition, they display a superparamagnetic behaviour favouring the colloidal stability. We have investigated the adsorption of phosphates using these RSNs and demonstrated that they can be used as phosphate recyclable adsorbents, extracted from the media by applying a magnet. In vitro experiments have been conducted in a home-made peritoneal dialysis model to evaluate the efficiency of dialysis performed model. 1. Chem. Mater. 19 (2007), 4494?4505 2. Chem. Eng. J. 256 (2014) 187?204 3. Nanoscale (2017), 9(1), 305-313

Resume : Many plastic materials offer an opportunity to decrease weight, while enhancing the efficiency of their products. Hence, the development of lightweight fillers for plastic formulations is on demand. In this work, starch was used to develop lightweight calcium carbonate-based fillers for low density polyethylene (LDPE) materials. Under a circular economy concept, starch and calcium carbonate (CaCO3) were recovered potato washing slurries and eggshells, respectively. Commercially available CaCO3 was used as reference. The influence of these fillers on optical, physicochemical, and mechanical properties of LDPE formulations was studied. CaCO3 recovered from eggshells shows a similar size (ca. 10 µm) than the commercial one (ca. 8 µm) and is 3% less dense. On the other hand, CaCO3/starch-based conjugates have higher particle sizes (ca. 60 µm) and are 15% lighter than the reference. When incorporated into LDPE formulations, CaCO3/starch-based fillers conferred a yellowish coloration to the LDPE materials, that may be related with the starch sensitivity to the temperature used on LDPE/fillers melt-mixing. When compared with the plastic produced using commercially available CaCO3, the CaCO3/starch-based fillers decrease in 5% the density of LDPE materials and increase their mechanical rigidity, which may be potentiated by the hydrogen bonding between starch and the LDPE network. Therefore, CaCO3/starch-based conjugates can be considered to develop lightweight LDPE materials. Acknowledgments: Thanks are due to the University of Aveiro and FCT/MCTES for the financial support of CICECO (FCT Ref. UID/CTM/50011/2019) and QOPNA (FCT UID/QUI/00062/2019) through national funds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement, and to the Portuguese NMR Network. FCT is also thanked for the Investigator FCT program (PF) and to the Scientific Employment Stimulus program (IG). The authors acknowledge to PLASTICOLIGHT (POCI-01-0247-FEDER-33848), financed by FEDER through POCI, to ?Isolago ? Indústria de Plásticos, S. A.? (PLASTICOLIGHT leader); and to ?Derovo? and ?A Saloinha, Lda.? for providing the wastes.

Resume : Curcumin, the active ingredient of turmeric (Curcuma longa), is very well known for its wide range of biological activities. Amongst them, its antibacterial and antibiofilm capacity are well-known, however hindered by its low water solubility and thus low delivery efficiency to the desired site. This work presents a valuable method for increasing curcumin?s antibiofilm activity via conjugation with silica nanoparticles. Specifically, Pseudomonas putida was used to produce model biofilms to assess the diffusion, delivery and antimicrobial/antibiofilm efficacy of the curcumin-functionalised nanoparticles (curc-NPs). Biofilms are known for their increased resistance against antimicrobials due to the existence of extracellular polymeric substances (EPS) and therefore represent an extra hurdle for curcumin delivery. The curc-NPs were shown to be stable both sterically and electrostatically and were more effective than free curcumin at the same concentration at disrupting pre-formed biofilms and impeding the proper development of P. putida biofilms. The bacterial cell viability of the biofilms was also significantly decreased. Furthermore, a proteomics study of extracted EPS matrices of biofilms grown in the presence of curc-NPs was carried out, and mechanistic insights of the action of this nanoparticle were acquired.

Resume : The formation of biofilms, bacterial communities enclosed in a self-produced matrix, raise the challenge to fight infections because the existence of the extracellular polymeric substances (EPS) largely contributes to the decrease of antimicrobial susceptibility. Methicillin-resistant Staphylococcus aureus (MRSA) is one of the most frequently occurring infections, whose treatment is mainly based on vancomycin (VAN) and daptomycin, with emerging susceptibility issues. Given the long timeline for novel drug development, repurposing existing drugs and improving antibiotic efficacy should be considered. Amongst the antibiofilm strategies currently being tested, nanoparticles (NPs) are showing promise as antimicrobial carriers. Here, mesoporous silica nanoparticles (MSNs) of different surface functionalization (bare-B, amine-D, carboxyl-C, aromatic-A) were investigated for VAN encapsulation and delivery, its entrapment in the EPS matrix and resulting decrease in cell viability of two clinical isolates of S. aureus, MSSA and MRSA. Negatively charged MSN-B and MSN-C encapsulated a higher concentration of VAN in comparison to positively charged MSN-D and MSN-A. All NPs tested effectively reduced cell viability, with a 3-6-fold decrease in viable cells for MRSA compared to free VAN. MSNs improved drug penetration and protected VAN from deactivation in the EPS matrix. Thus, allowing the use of lower VAN concentrations, while increasing its local concentration delivered to the cells.

Resume : According to the US National Institutes of Health, over 60% of all human microbial infections are caused by biofilms. Today, biofilm formation by hospital strains by bacteria is a serious threat to practical health care. We conducted a study aimed at the effect of nano-materials on the effect of film formation by reference and clinical strains of microorganisms. Screening studies were conducted to detect changes in the effect of film formation on objects which coated nano-TiO 2 and basalt tuff. With fingerprint steklyshek control samples coated with acrylic paint only basalt and tufa culture S . aureus ATCC 25923 was seeded from 1.31 × 10^2 CFU / cm ^2 to> 3.0 × 10 ^2 CFU / cm^ 2 , the concentration of bacterial cells in the extracted fluid from the surface of the glasses or remained as in the working suspension of 10 ^5 cells / ml , or increased to 10 ^9 cells / ml. As for E . coli ATCC 25922 , the data samples from the surface of vysivalys 1,22 × 10^ 2 CFU / cm ^2 to> 3,0 × 10^ 2 CFU / cm ^2 , and the concentration of viable microorganisms in the liquid from the surface ranged from 10 ^6 cells / mL, or grew to> 10 ^9 cells / ml. The next step in establishing the effect of nano-TIO 2 on the adhesive and colonization properties of the reference cultures was demonstrated. Addition to the roofing material of nano-TIO 2 from 0.05% to 2% (samples No. 6-No. 9) significantly changed the adhesive properties, so, from the surfaces of these samples sown 1.14 × 10^2 CFU / cm 2 to 0.6 × 10 ^1 CFU / cm 2 , respectively, on E . coli ATCC 25922 , from surface samples from ?6-9 0,98 × 10^2 CFU / cm^2 to 0,22 × 10^2 CFU / cm^2 . The experiment found that nano-based materials affect the ability of microorganisms to form biofilms , which can be used in medical practice.

Resume : The gelling ability of starch has been explored in organic/inorganic formulations to develop porous materials [1]. On the other hand, the inherent high density of calcium carbonate (CaCO3), common filler in plastic industry, limits its application for the development of lightweight plastics. To overcome this drawback, in this work, the influence of gelatinize eggshell powder/starch conjugates assisted by microwave irradiation on optical, morphological, and physicochemical properties was studied. For comparison, a conventional gelatinization process and commercial CaCO3 were used. Starch was recovered from potato washing slurries and eggshells powders were used as the CaCO3 matrix. When assisted to microwave irradiation, gelatinized eggshell powder/starch conjugates show a whiteness level, chemical profile and crystalline structure comparable with the commercial CaCO3. These conjugates have higher particle size and specific surface area than the commercial CaCO3. However, their density is 24% lower than the reference. By gelatinizing eggshell powder/starch conjugates through conventional heating only 18% of density is decreased. Therefore, the microwave irradiation seems to potentiate the density decrease of eggshell powder/starch, offering a new strategy to develop lightweight fillers for plastic formulations. Acknowledgments: Thanks are due to the University of Aveiro and FCT/MCTES for the financial support of CICECO (FCT Ref. UID/CTM/50011/2019) and QOPNA (FCT UID/QUI/00062/2019) through national funds and, where applicable, co-financed by the FEDER, within the PT2020 Partnership Agreement, and to the Portuguese NMR Network. FCT is also thanked for the Investigator FCT program (PF) and to the Scientific Employment Stimulus program (IG). The authors acknowledge to PLASTICOLIGHT (POCI-01-0247-FEDER-33848), financed by FEDER through POCI, to ?Isolago ? Indústria de Plásticos, S. A.? (PLASTICOLIGHT leader); and to ?Derovo? and ?A Saloinha, Lda.? for providing the wastes. References: [1] A. F. Lemos and J. M. F. Ferreira, Mater. Sci. engeering, 11 (2000)

Resume : Opto-stimulation of semiconductor-biointerfaces provides efficient pathways towards eliciting neural activity through selective spectral excitation. In visual prosthesis, tri-colour excitation capability, is the key to restoring full-colour vision. Among organic semiconductor materials, donor?acceptor molecules have the most promising properties due to excellent light absorption, high stability and good solubility in organic solvents. Varying the donor and acceptor functionalities allows fine tuning of their absorption bands. These carbon-based molecules bear intrinsic affinity to biological systems, demonstrate excellent photoresponses, electronic and ionic conductivity, and allow intimate interface with liquid bioenvironment. We demonstrate tri-colour optoelectronic devices based on solution-processable conjugated donor-acceptor molecules with absorption in red, green and blue spectral regions, mimicking the absorption of human retinal cones. Photo-response is studied via interfacing with biological electrolyte solution and using long-pulse, narrow-band excitations, where both photo-voltage and photo-current responses show clear signatures of capacitive charging at the electrolyte/device interface. We further explore ink-jet printing to reproduce individual photo-pixels with red, green and blue absorption characteristics, with small diameters of 35 to 45 microns. We discuss the suitability of organic semiconductors for potential medical applications as retinal bio-engineered prosthesis for the restoration of human vision, and evaluate prospects of wider, colour-selective excitations of bio-interfaces. (This work was supported by Russian Science Foundation grant 19-73-30028).

Resume : Neural activity can be measured or stimulated using electrodes that can be improved with nanotechnology advances. In this work, we propose the use of template-assisted electrodeposition technique to obtain, in a reproducible way, nanostructured metallic surfaces that can work as neural electrodes. On one hand, planar electrodes are used in extracellular experiments and medical applications to register or stimulate neural activity. In the context of the ByAxon project, our results on the fabrication of low-disturbance flexible nanostructured planar electrodes based on vertical metallic nanowires standing over a flexible Au base will be presented. We have obtained low-impedance electrodes by electrodeposition using anodic aluminium oxide templates fabricated at the laboratory, controlling the geometry of the electrode?s nanostructured surface. Biocompatibility studies with these electrodes showed proper neural cell adhesion, growth and differentiation. On the other hand, to perform intracellular in vitro recordings, patch-clamp technique is the most extended one. However, it damages the cell due to perforation size and medium exchange reducing life time when measuring. In this work, our progress in the fabrication of sharp nanostructured metallic electrodes based on the process described above, in order to improve the existing intracellular recordings, will be shown. Work funded by H2020 R&D programme under grant agreement No. 737116 and I D I project DPI2017-90058-R

Resume : Thanks to their versatility, proteins are ideal building blocks for functional materials. Controlled protein assembly is necessary for bottom-up fabrication of biomaterials.[1] Many strategies can be employed to achieve protein assembly, like computational design of protein interfaces, supercharged proteins or tethered linkers.[1] The use of macrocyclic receptors is a viable alternative. Macrocyclic receptors, like cucurbiturils or calixarenes, recognize patches on protein surfaces and induce assembly / crystallization by bridging two or more proteins. This transferable approach has been demonstrated in different proteins and does not require expensive protein functionalization or the use of designed proteins.[2-3] Metal coordination is another directional interaction employed to facilitate protein assembly.[4] We postulated that macrocycle recognition coupled with metal coordination will increase the control over assembly design. To demonstrate this idea, we tested two different protein model systems: a β-propeller lectin and a highly cationic small protein. Our research paves the way for new biohybrid materials. [1] Luo, Q.; Hou, C.; Bai, Y.; Wang, R.; Liu, J., Chem. Rev., 2016, 116, 13571–13632. [2] Rennie, M. L.; Fox, G. C.; Pérez, J.; Crowley, P. B., IUCRJ, 2019, 6, 238-247. [3] Guagnini, F.; Antonik, P. M.; Rennie, M. L.; O’Byrne, P.; Khan, A. R.; Pinalli, R.; Dalcanale, E.; Crowley, P. B., Angew. Chemie Int. Ed., 2018, 57, 7126–7130. [4] Bailey, J. B.; Zhang, L.; Chiong, J. A.; Ahn, S.; Tezcan, F. A., J. Am. Chem. Soc., 2017, 139, 8160–8166.

Resume : Micro and nano-biointerface has been emerging as a key topic for tissue regeneration, basic biology sciences, and medicine in recent years. Understanding the influence of specific characteristics of materials at biological interfaces can bring advantages to designing two and three-dimensional biointerfaces able to guide cell fate in a controllable and accurate way. By an appropriate combination of fabrication technologies and particular materials properties, effective design tailored supports and scaffolds with controlled micro nanoscale topography and chemistry can be achieved towards controlled cellular microenvironments as a powerful tool for fundamental biology studies. Within this context, in this work, laser processing of micro-structured biomaterials ( i.e ceramics, polymers, PDMS replica starting from laser processed surfaces) with convex and concave topographies for evaluating the role of materials surface topography on different mammalian cell lines responses are presented. For example, laser direct texturing and Matrix-Assisted Pulsed Laser Evaporation -MAPLE were used for modulating specific characteristics of biointerfaces, which roles were studied by investigating the biocompatibility and biological reactions induced by new materials, especially the immune response and the capacity for bone regeneration and hepatocyte-like cells differentiation. The physicochemical characteristics of the microstructured surfaces, along with the in vitro analyses, suggest that our designed interfaces represent an efficient way to tackle the design of implant surfaces or smart interfaces for a wide range of biomedical applications.

Resume : Additive manufacturing is also known as 3D printing, is enabling the production of structured functional materials and has the potential to close the gap between discoveries and manufacturing by providing an effective path toward favorable device cost and performance. Central to many promises of 3D printing is to overcome the limitations of conventional device productions to allow freedom of design and provide new functionality while substantially lower the materials cost and energy. Although, additive manufacturing is coined as the revolutionary manufacturing technique of choice, by mimicking nature?s pathway in creating functional systems, perhaps the most important neglected aspect which severely overshadows its promises is the lack of a platform to bridge the gap between the nano-world to the macro-world, which nature elegantly executes. This calls for the convergence of typical 3D printing techniques with a resolution at the molecular level to effectively exploit the nanoscale properties of individual building blocks in the final architecture. If this achieved, 3D printing can be effectively used to print complex multifunctional electrodes containing both scaffolding and active materials for batteries, supercapacitors and electrocatalysis applications. Biological systems implement anisotropic molecular building blocks and their remarkable self-assembling properties to achieve liquid crystal mediated complex structural arrangements and patterns. Following this model, we use self-assembly to impart the fine-tuning required for the design-freedom of architecturally complex systems at the nanoscale with intricate patterns within 3D printed constructs. The printing ink prepared from a mixture of liquid crystals (LC) of nanocellulose (NC) whiskers and large sheets of graphene oxide (GO), which shows highly ordered laminar organization not inherently present in the source materials. The bioinspired 3D printing approach exemplifies how the self-assembly approach in the traditional 3D printing processes can unlock the potential of individual constituent phases to print macroscopic architectures with nanoscopic arrangements. Our demonstrations will serve as a roadmap in additive manufacturing technologies for extensive development ranging from the choice of materials in nanoscale, design, and construct to device performance.

Resume : Dental caries, a critical issue faced by children in poor communities, can credibly be arrested by silver diamine fluoride (SDF), a popular cariostatic agent, though leaving behind black stains on the teeth. To rectify this issue, current work aims to develop polyelectrolyte-based (involving electrostatic interactions with positive silver ions) formulation, comprising of nano silver fluoride (PE-NSF). UV-Vis spectroscopy was used to characterize the PE-NSF, depicting formation of silver nanoparticles by a distinct peak. Further, the particle size and microstructure were analyzed by DLS and TEM. Carious primary molars were utilized for the extraction of dentin specimen and sorted based on tooth size and category, to which SDF and PE-NSF were applied for assessing the staining, until a period of 7 days. Teeth in the PE-NSF were unstained while SDF group were black-stained after 7 days incubation time. Moreover, the arrested caries by PE-NSF were also comparable to that of SDF. The morphological and elemental investigations of the teeth samples were examined by SEM, EDX, and TEM for study of presence of collagen in the arrested lesions and remineralised crystalline apatites. Therefore, the PE-NSF can serve as a potential candidate for the dental caries treatment, without staining the teeth.

Resume : The present study explored wear and biocompatibility characteristics of polypropylene (PP)/ periwinkle shell particulates (PWS) composites for dental implant application. Wet-sliding the stainless steel ball against specimen disc revealed the abrasive wear behaviour of the composites under load and linear speed of 5N and 10 cm/s respectively. In the wear tests, the specimens were wetted with simulated human saliva with and without sodium fluoride (NaF) additive. On the other hand, a mouse specimen was used to carry out a biocompatibility test. The composite demonstrated superb wear resistance at 40 and 50wt% reinforcement loading. Further, results showed that wear rate decreased considerably with increasing PWS content. Higher wear rate was noted on composites under condition of simulated human saliva with NaF addition. The biocompatibility test reveals that developed composite is harmless to the living tissues. Thus, PP/PWS composites could be recommended to be used as dental restorative material.

Resume : To realize high-performance thin-film transistors, solid-phase crystallization (SPC) of Ge films on insulators has been widely investigated, which is a simple method to directly form polycrystalline thin films on insulators. Recently, we succeeded in increasing the grain size of the Ge thin film on the glass substrate by controlling the density of amorphous Ge, which is the precursor of SPC, and have continued to update the highest record of mobility of the low-temperature synthetic film [1,2]. In this study, we develop this SPC-method onto plastic substrate. In the experiment, GeO2 underlayer was sputtered on both SiO2 glass and plastic substrates. After that, amorphous Ge precursors were prepared by molecular beam while heating the samples at 150 °C. Finally, the samples were then loaded into a conventional tube furnace in a N2 atmosphere and annealed (375 °C, 150 h) to induce SPC. As a result, SPC-Ge formed on a plastic has almost the same crystal grain size as that on a glass. By examining the electrical properties of substrate dependence of Ge layer, we found that there is almost the same tendency of electrical properties between the samples on plastic and glass substrates. With the above, we performed post annealing (500 °C, 5 h) in order to reduce the grain boundary barrier and the impurity scattering, and achieving hole mobility of 680 cm2/Vs for Ge thin film on plastic substrate. It is the highest value to date among those of semiconductor layers directly formed on insulator and is a result for exploiting excellent flexible devices. [1] K. Toko et al., Sci. Rep. 7, 16981 (2017). [2] T. Imajo et al., Applied Physics Express 12, 015508 (2019).

Resume : Antennas are an essential component of next generation wearable electronics for wireless communication. It is highly desirable to develop a robust self-healable antenna to maintain the integrity and function of the device because the wearable devices are becoming ever-thinner and smaller, making them subject to serious wear and damage during the body bending or stretching. However, it has been a significant material challenge as the integral antenna can not be exposed to external stimulus such as heat, light and chemical agents without damaging the devices. Herein, we design a latex-polyelectrolyte coacervation (LPC) system compounded with conductive filler to form a printable conductive paste which exhibits robust toughness, stiffness, extensibility, high electrically conductivity, one-step printability and self-healing capability simultaneously. The formation of polymer network via electrostatic interaction and hydrophobic interaction within antenna provide a self-healing mechanism via the absorption of moisture in the ambient air. The LPC system is promising for broad applications in self-healable stretchable electronics.

Resume : In the present study, we have biosynthesized ZnO NPs and investigated the mechanism of anti-inflammatory action of the nanoparticles in both in vitro and in vivo models. In the in vitro model system, RAW 264.7 murine macrophages were pre-incubated with ZnO NPs and the effect of NPs on the lipopolysaccharide (LPS)-induced activation of nuclear factor-kappa B (NF- κB) pathway was evaluated. Results show that LPS mediated increase in expression NF- κB pathway was downregulated by an increase in expression of inhibitor of kappa B alpha (IκBα) in NP treated cells in a dose-dependent manner. The anti-inflammatory potential of ZnO NPs was also evaluated in Carrageenan induced mice paw edema model. Administration of ZnO NPs to mice, prevented Carrageenan induced mice paw edema and also suppressed the expression of pro-inflammatory mediators like interleukin-1 beta (IL-1β), interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2). Histological analysis of mice paw tissue section clearly indicated a reduction in leukocyte and neutrophil extravasation to the tissue space in mice paw that was pre-treated with ZnO NPs. Present findings give us an insight into the ZnO NPs mediated anti-inflammatory action.

Resume : Cervical cancer is the most common malignancy suffered by women worldwide in the female reproductive system. The chemotherapeutic treatment using anticancer drugs are developed recently, but they lack delivery to the targeted tumour tissues. The commonly used anticancer drug paclitaxel is highly efficient against various cancer types, but due to its low solubility the enhancement of its property decreases. Recent advances includes nanotechnology based combinatorial drug delivery systems that offer enhanced pharmacokinetic property due the EPR (enhanced permeable retention), the larger surface area to volume ratio in nanoparticles, it also helps in adsorbing large amount of drug and act as a drug carrier. The combination of nanosystems aids in active or passive drug delivery through the cell membranes via endocytosis. In particular selenium nanoparticles is a well established chemotherapeutic agent due to low toxicity to the normal tissues, when compared to other nanosystems. The selenium nanoparticles act as both prooxidant in the presence of cancer tissues by producing ROS which eventually causes oxidative stress, mitochondrial damage, alter the genetic arrangements of the cancerous tissues, they are also major component of many antioxidant enzymes that also function at protecting from tumour like GSH (glutathione), selenomethioninecystien (recent established amino acid), theoredoxin (Trx) and so on. They act as antioxidant agent for normal tissues by scavenging ROS, regulating the DNA repair proteins, and protecting the damages caused by oxidative stress. In this paper more emphasis is done on the green synthesis of selenium nanoparticles to avoid the utilization of external harmful chemicals. The precursor used for the reduction of the sodium selenite which itself it a harmful chemical which was traditionally used as anticancerous agent, are Mucuna pruriens seed extract which is also a traditional medicine against various cancer types. The extract is used as a bioreductive catalyst which also helps in stabilization of the nanoparticle development. The biosynthesized SeNPs are optimized using BB design for evaluating the optimum particle size and process variable. The optimized SeNPs are then coated with chitosan which acts a biodegradable linker against anticancer drug paclitaxel. The combinatorial nanosystem is evaluated for its anticancerious activity against HeLa cancer cells. This innovative strategy can help in overcoming the drawbacks faced by chemotherapeutic drugs with low solubility, delivery to the targeted sites, highly biodegradable and low toxicity.

Resume : INTRODUCTION Bone tissue can be damaged by aging, some diseases or some accidents. Critical bone injuries and tissue losses have led to the need for the use of various biomaterials in the clinic. Firstly, metals such as cobalt-chromium alloys, stainless steel, titanium alloys have been used in biomedical applications. However, although these biomaterials support bone repair, they are not suitable for the purpose of supporting new bone formation, because they lack biological resorption characteristics. Therefore, many researchers oriented to other alternatives. One of these alternatives is the production of bioceramics such as hydroxyapatite (HA) and tricalcium phosphate. Many studies have shown that bioceramics containing silicon (Si), calcium (Ca) magnesium (Mg) have high bioactivity, biocompatibility, and strong mechanical properties. Therefore, they can be used in bone repair and regeneration as scaffolds with polymers such as polycaprolactone (PCL). The aim of study is to investigate potential of PCL/HA/Akermanite(AKR) and PCL/ carbonated hydroxyapatite (CHA)/AKR fibers produced by electrospinning method for bone tissue engineering. MATERIALS AND METHODS HA was synthesized by microwave irradiation method while CHA was synthesized by nanoemulsion technique. AKR was fabricated vis sol-gel method. After characterizations of bioceramics such as X-Ray Diffraction (XRD) and Fourier Transform Infrared (FT-IR), and bioactivity tests in simulated body fluid (SBF), scaffolds were producing by wet electrospinning. PCL using carrier material and was dissolved in ethanol. After optimization of some parameters such as voltage and flow rate, PCL/HA/AKR and PCL/CHA/AKR fibers were produced. Then, in vitro bioactivity tests of scaffolds were performed in SBF for 1,7 and 14 days to determine apatite layer formation. At the end of the immersion times, scaning electron microscopy (SEM) analysis was used for imaging apatite layers on the fibers. Also, elemental analysis (EDS) was done. Furthermore, cell adhesion, proliferation and osteogenic activity were studied with Saos-2 cells. CONCLUSION HA, CHA and AKR were synthesized respectively by microwave irradiation, nanoemulsion and sol-gel methods. Characterization techniques such as XRD and FT-IR proved that bioceramics produced successfully. In vitro bioactivity experiments showed that there are spherical apatite layer formations on the PCL/HA/AKR and PCL/CHA/AKR fibers produced by wet electrospinning. Moreover, cell proliferation and osteogenic activity of Saos-2 cells on the scaffolds were good.

Resume : When fluorometric imaging of concentration change of potassium (K ) and/or sodium (Na ) ion due to channel on a cell surface is realized with molecular probe, we will understand the working of these ions as a whole in a cell and the relationship between their abnormality and specific diseases such as channelopathy. Although crown ether type fluorescence probes have been developing in this purpose, it is very difficult to do fluorometric imaging of K or Na specifically under homologues aqueous medium. Under such circumstances, we have developing new type of probe consisting guanine tetraplex (G4) forming sequence oligonucleotide with K or Na carrying two chromophore pairs of Förster resonance energy transfer (FRET), which named potassium or sodium sensing oligonucleotide, PSO or SSO, respectively [1,2]. Additional attachment of biotin with PSO realized fluorometric imaging of cellular cytoplasm K in a living cell and monitored K efflux from cell under apoptosis process [3]. As a next stage, we are tried to localize PSO on a cell surface and monotone K concentration change on a cell surface. Here, we will introduce our new approach to achieve this attempt, where the lipid-modified oligonucleotide carrying FAM (1) on a cell surface hybrids with the G4-forming oligonucleotide carrying TAMRA (2) resulting localization of PSO function on a cell surface. Here, we will discuss our approach with the related results. [1] B. Juskowiak, S. Takenaka, FRET in the studies of guanine-quadruplex, Fluorescent Energy Transfer Nucleic Acid Probes: Designs and Protocols (Methods in Molecular Biology), (Didenko, V. V. Ed.), Humana Press, Inc. (Totowa, NJ), pp. 311-341 (2006). [2] S. Sato et al., Anal. Sci., 35, 85-90 (2019). [3] K. Ohtsuka et al., Chem. Comm., 48, 4740-4742 (2012). S. Takenaka, Curr. Protoc. Nucleic Acid Chem. 62, 8.9.1-8.9.9 (2015).

Resume : Triboelectric nanogenerators (TENGs) convert mechanical energy into electrical energy, providing the possibility of self-powered implantable electronic devices. However, most implantable electronic devices still require an external power source. In addition, TENGs must have outstanding biocompatibility, biodegradability, and controllable degradation rate to prevent the need for a second surgery and avoid an inflammatory response. In this work, a silk nanofibril (SNF)-based bio-TENG is fabricated using a nascent SNF film (SNFF) and regenerative silk fibroin film (RSFF). To maintain the original meso/nanoscale structure of silk, SNFs with a thickness of 0.38 nm are directly exfoliated from natural silk. RSFF and SNFF have different microstructure and work functions. The output performance of the bio-TENG with the maximum voltage, current, and power density (PD) reach up to 41.6 V, 0.5 μA, and 86.7 mW/m2, respectively. The lifetime of the TENG depends on post-treatment of the RSFF package. The raw materials of the proposed TENG, including silk and magnesium (Mg), are completely biodegradable and biocompatible in vitro. With its high sensitivity and the ability to generate power from just a human pulse, the all silk-based bio-TENG may be an attractive power source for implantable self-powered electronic devices, such as pacemakers and implantable sensors.

Resume : Both high static contact repellency and resistance to liquid drop impact are quite necessary to achieving a high-performance omniphobic surface. The cuticles of springtails, a small insect in nature, have both of these features, which result from their hierarchical structure composed of primary nanostructures on secondary microgrooves. Despite intensive efforts, none of the previous reports that were inspired by the springtail were able to achieve both high static repellency and pressure resistance simultaneously due to a general trade-off between these features. We demonstrate for the first time a springtail-inspired superomniphobic surface showing both features by fabrication of a hierarchical structure consisting of serif-T–shaped nanostructures on microscale wrinkles. Our biomimetic engineering yielded a surface having high repellency to diverse liquids, from water to ethanol, with an apparent contact angle above 150°. The surface was also able to show extreme pressure resistance from the impacts of diverse liquid drops, which is the best pressure resistance on omniphobic surface ever reported.

Resume : Herein, we report a biogenic route of hydroxyapatite nanoparticle (HANP) synthesis either in presence of the whole cell (WC) of the lactic acid bacteria (LAB) Lactobacillus rhamnosus GG or a malonic acid amphiphile (MA). HANPs were generated by in situ precipitation and the characteristic peaks at 3568, 1461, and 1041 cm-1 observed in FTIR analysis and the prominent peaks at around 2θ = 26° and 2θ = 33° in PXRD analysis revealed that the LAB cells and MA could generate hydroxyapatite phase. FESEM revealed that WC-HANPs were spindle-shaped and 70-110 nm in size while MA-HANPs were spherical and 22-27 nm in size. HRTEM indicated that the lattice distance for WC-HANPs and MA-HANPs was 0.28 nm and 0.29 nm, respectively, while SAED confirmed the crystallinity of HANPs. TGA analysis indicated degradation of WC-HANPs and MA-HANPs from 20°C to 800°C, with 83% and 87% residual mass, respectively. BET analysis indicated that WC-HANPs and MA-HANPs had a surface area of 170.47 m²/g and 90 m²/g, respectively, and an average pore size of 4.9 nm and 4.04 nm, respectively. Both the HANPs were non-toxic to cultured osteosarcoma MG-63 cells. Fluorescence microscopic analysis revealed that the MG-63 cells grown in presence of HANPs appeared elongated, suggesting that HANPs likely support bone cell differentiation. The biogenic route of HANP synthesis outlined herein is an interesting prospect to generate potentially biocompatible nanomaterials for tissue engineering applications.

Resume : Incorporating hydrophilic tetraethylene glycol with saddle-shaped nanographene make water-soluble warped nanographene (WNG) has good solubility in organic solvents and water. It exhibits strong green-yellow fluorescence, high photostability, and low cytotoxicity. The aforementioned properties imply that water-soluble WNG is applicable to live-cell imaging. Subsequently, water-soluble WNG was applied for HeLa cell imaging. The results indicated that water-soluble WNG internalized in HeLa cells and accumulated into the lysosome as aggregates. During live-cell imaging by water-soluble WNG, we serendipitously discovered that the HeLa cells stained with water-soluble WNG could be killed by selective laser irradiation. In the presence of 5.0 mM of water-soluble WNG, the light irradiated HeLa cell shrunk, generated blebs, and finally died. Moreover, dose-depended cell viability is observed. The cell viability was 98% in the presence of 0.01 mM of water-soluble WNG. Upon increasing the concentration of water-soluble WNG from 0.01 to 1.0 mM, a dramatic decrease in cell viability was observed, and 91% of the cells were killed in the presence of 1.0 mM water-soluble WNG under irradiation. Using 5.0 mM water-soluble WNG, almost no cells survived under the irradiation. In contrast, even in the presence of water-soluble WNG, no obvious change in cell morphology and viability was observed without light stimulation. Although the mechanism is unclear, the relatively high efficiency of the singlet oxygen generation of water-soluble WNG may contribute to its HeLa cell death.

Resume : Noble metal nanomaterials hold the promise to shift the current medical paradigms for the treatment and diagnosis of several diseases, among which neoplasms and infections, due to their peculiar chemical, physical and physiological behaviors. Despite the massive efforts, treatments based on inorganic nanomaterials are mainly at the preclinical stage, due to the body persistence issue. Indeed, non-biodegradable materials persist within excretion system organs for long-term: that is not acceptable for exogenous drugs. The most recent progresses in the design, production and application of noble metal nanomaterials able to escape from the organism after the designed action will be discussed together with their biokinetics, and biosafety. The research leading to these results has received funding from AIRC under MFAG 2017 – ID 19852 project – P.I. Voliani Valerio.

Resume : In vivo thermometry is an emerging area of research to understand the temperature regulation within and between the organs and to describe the intricate cellular metabolic processes. Highly green luminescent gold nanoclusters (Au NCs) have been successfully implemented as potential sensors for temperature measurement in vivo because of their small size, biocompatibility, quick equilibration with temperature and most importantly their response reflect the thermal environment in the physiological temperature range. This thermoresponsive fluorescence lifetime based nanoprobe based on the supramolecular host-guest recognizition employing 6-aza-2-thiothymine and L-arginine (L-Arg) shows selective cytoplasm staining and robust response to temperature. Subsequently, fluorescence lifetime imaging microscopy (FLIM) has been employed to elucidate intracellular nanothermometry inside living cells. In depth understanding of protein-Au NCs interaction offer a promising avenue to rationally design target-specific fluorescent biolabeling agent. Because of the small surface area of the Au NCs, these probes open up the new possibility of combining therapeutic moieties having the specific cytoplasm targeting capability and simultaneously monitor the temperature assisted drug- delivery/release.

Resume : Recently, nanocellulose has gained much attention as a potential reinforcing material in the field of composites owing to its excellent mechanical, biodegradable, renewable, and biocompatible properties. Cellulose nanocrystals (CNCs), which combine natural abundance and excellent mechanical properties, are a promising candidate for use as polymer reinforcement agents. CNCs are employed in a variety of fields to enhance the mechanical properties of products such as cosmetics, pharmaceuticals, paper coatings, and additives in paper and paperboard. The high density of hydroxyl groups provides the hydrophilic properties of these materials, making them also suitable for the production of hydrogels. However, because of their hydrophilic nature, CNCs are mainly used to control the hydrophilic properties and improve the mechanical properties of hydrophobic polymers, especially synthetic polymers. On the other hand, in the case of hydrophilic polymers, an additional physicochemical cross-linking process is required because CNCs only affect the mechanical properties of composite materials. In this work, dual functionalized-CNCs as a nanofiller was used to develope a gelatin-based nanocomposite film with enhanced mechanical properties and hydrolytic stability . Through the sodium periodate oxidation reaction, C2-C3 cleavage of cellulose molecules was generated and the aldehyde groups were introduced on these carbon atoms. Using dialdehyde CNCs, interfacial covalent bonding was formed between the aldehyde group of the CNCs and the amine group of the gelatin molecule through a nucleophilic addition reaction. To investigate the effect of the dialdehyde CNC content on the properties of the biocomposite, the mechanical and physicochemical properties and the hydrolytic stability of the fabricated biocomposite films were studied using various analysis techniques. The bi-functional CNCs, which can have both cross-linking and reinforcing effects, would expand the fabrication and exploration of high-performance biopolymer nanocomposites. The gelatin-based nanocomposite film developed by this strategy has greatly improved mechanical properties and hydrolytic stability, which suggests that gelatin can be used not only as a hydrophilic polymer but also as a universal polymer.

Resume : To increase bone regeneration around a titanium implant, nanopattern surfaces with 10 nm nanopores in 120 nm dimples were produced by electrochemical nanopattern formation (ENF). The ENF surfaces were obtained by removing the TiO2 nanotube layers prepared by an anodization process. To determine the effect of the ENF surface in vitro, cell proliferation assays, alkaline phosphatase (ALP) activity assays, Alizarin red staining, western blotting, and immunocytochemistry were performed. Atomic force microscopy and scanning electron microscopy analysis showed that the ENF surface had an ultrafine surface roughness with highly aligned nanoporous morphology. In vitro, human mesenchymal stem cells exhibited increased cell proliferation and enhanced expression of osteogenic molecules such as ALP, osteopontin, and osteocalcin on ENF surfaces compared to the TiO2 nanotube surfaces. Therefore, ENF is a promising technique for coating osteointegrative implant materials.

Resume : Indoxyl sulfate (IS) has been reported to not only accelerate the progression of chronic kidney disease (CKD), but also increase the risk of cardiovascular disease by increasing the oxidative stress of CKD patients. Current haemodialysis facilities are immobilized due to huge dialysis machine and dialysate bag. Some wearable artificial kidney (WAK) devices are still based on diffusion principles, which could not fundamentally solve the problem of portability. We report on a novel IS absorbent material based on biocompatible polycaprolactone-chitosan (PCL-CS) nanocomposite fibrous structure. This composite absorbent material has a high internal surface to volume ratio so as to greatly increase the interaction between the IS and chitosan, which exhibits character of high binding affinity to IS molecules. The PCL-CS absorbent material was fabricated by 2D-controlled close-range electrospinning. The surface morphology and chemical composition were characterized by a combination of scanning electron microscopy (SEM) and thermogravimetric analysis (TGA). The IS molecule absorption of the PCL-CS absorbent was quantitatively evaluated. This novel nanocomposite absorbent may provide new sights for the removal of metabolic toxins in a portable way.

Resume : Au decorated aligned ZnO nanorods are synthesized on the Ti substrate by the silane coupling agent-assisted seed layer formation and hydrothermal process with the following magnetron sputtering of gold nanoparticles. The Au@ZnO systems inactivate about 80% of Escherichia coli in the first 1h culture in the dark through an extracellular electron transfer mechanism instead of ROS production and zinc ion releasing. Electrons on the respiratory chains of the bacterial membrane transfer to the surface of the materials, making bacteria lose electron until death. At the same time, the transferred extracellular electrons convert into the bacterial current by the electrochemical workstation, primarily demonstrating the property of the materials to function as a sensor of bacteria counting and status observation. This work sheds light on the detailed understanding of antibacterial behaviors of ZnO-based materials especially at the early stage of bacteria-material contact and provides insights for the designing of devices with both antibacterial and detection applications.

Resume : Developing materials that can absorb large amounts of strain without fracture or significant degradation in their electronic properties is important to realize stretchable electronics. Here, stretchable conductors made from reduced graphene oxide/polydimethylsiloxane (r-GO/PDMS) composite are fabricated to achieve stable resistance changes under uniaxial stretching. By controlling the weight fraction of GO in water, highly aligned and porous GO structure is obtained over 0.5 wt% of GO solution. After thermal and chemical reduction of GO to r-GO film, PDMS is infiltrated into pores of the film to make free-standing and elastic composites. Electrical percolation of r-GO in the composite is achieved at the r-GO concentration over 0.3 wt% along with improvement of electrical conductivity. However, highly aligned r-GO/PDMS composite only exhibits notable suppression of resistance change under the large deformation of 100% strain. The resistance change of 0.3 wt% r-GO/PDMS composites at 100% strain is over 7 times higher than that of 0.7 wt% r-GO/PDMS composites, exhibiting the dramatic effect of r-GO alignments. Even after repeated stretching/releasing cycles, the variation in resistance from 0 to 70% of strain is stable. The stretchable conductor based on the aligned r-GO/PDMS composite was successfully applied as a resistive strain sensor.

Resume : Nowadays, diabetes became a serious problem since everyday 400 million people face with it. Following that, extensive research works towards the enzymatic electrochemical biosensors are undertaken since those devices can selectively monitor glucose level in human body fluids. In this work, preparation method and electrochemical activity of the enzyme-functionalized Au-Ti electrode are presented. Firstly, the conductive platform was fabricated via anodization process of Ti and further chemical etching that results in regularly distributed nanodimples. Secondly, the thin Au film sputtering followed by the thermal annealing leads to the Au nanoparticles formation in the host Ti hollows revealed by scanning electron microscopy. Thirdly, the surface of obtained material was modified with glucose oxidase by the hybrid immobilization route. The first layer was the self-assembled organic monolayer composed of HSC11H22EG6OCH2COONHS chains. Then, GOx enzyme was anchored via the N-hydroxysuccinimide ligand using the cross-linking immobilization route. Basing on the cyclic voltammetry measurements performed in PBS the sensitivity of 43.926 μMcm-2mM-1 was reached within glucose concentration range of 0.006-2.345 mM while the limit of detection was as low as 5.331 μM. Additionally, the measurements in artificial sweat and saliva as well as human serum were carried out to show the performance in the real conditions. Research is financed by NCBR via LIDER/2/0003/L-8/16/NCBR/2017 grant.

Resume : Nanosized zinc oxide is gaining importance in the biomedical field due to its commendable antibacterial efficacy. The increased specific surface area of the nanoparticles ensures enhanced particle activity, hence proving itself to be more effective than the bulk sized particles. The fluorescence property of zinc oxide arised due to defects and its use in biomedical field is recently being explored. In this work, shape controlled fluorescent zinc oxide nanoparticles was synthesized by a facile and novel wet chemical technique. Morphological and physico-chemical characterization of the nanoparticles were performed in order to affirm structural and functional aspects of the nanoparticles. Further, bactericidal activity of the 30 nm sized ZnO nanoparticles were tested against B. subtilis and E. coli. It was observed that 100 ppm conc of the nanoparticles were able to demonstrate 99% (5 log reduction) in bacterial colony size in 6 h of incubation time. Similar results were also witnessed in zone of inhibition, growth curve analysis, DNA leakage assay and live-dead assay, thus confirming bactericidal efficacy of the nanoparticles. Further, in vitro cytocompatibility was also performed with L929 fibroblast cells in order to evaluate toxicity profile of the nanomaterial. The excellent bactericidal efficacy coupled with low toxicity profile renders the fluorescently active sub-50 nm sized ZnO nanoparticles as an excellent alternative for next generation non-invasive biomedical applications. References 1. Ray, Preetam Guha, et al. "Sonication Assisted Hierarchical Decoration of Ag-NP on Zinc Oxide Nanoflower Impregnated Eggshell Membrane: Evaluation of Antibacterial Activity and in Vitro Cytocompatibility." ACS Sustainable Chemistry & Engineering 7.16 (2019): 13717-13733. 2. Alekish, Myassar, et al. "In vitro antibacterial effects of zinc oxide nanoparticles on multiple drug-resistant strains of Staphylococcus aureus and Escherichia coli: An alternative approach for antibacterial therapy of mastitis in sheep." Veterinary world 11.10 (2018): 1428.

Resume : Like many other open systems in nature, living organisms are replete with rhythmic and oscillatory behaviour at all levels, to the extent that oscillations have been termed as a defining attribute of life. Recently, we have started to investigate the “bottom-up” construction of peptide-based networks that display bistable behaviour and oscillations. We have utilized replicating coiled coil peptides, which have already served to study emergent phenomena in complex mixtures. In this talk, we will first describe the kinetic behaviour of coupled oscillators, producing various functions such as logic gates, integrators, counters, triggers and detectors.[1] These networks were also utilized to simulate the Kai-proteins circadian clocks, producing rhythms whose constant frequency is independent of the input intake rate and robust towards concentration fluctuations.[2] Then, we shall disclose our recent experimental results, showing for that the peptide replication process also lead to bistability in product equilibrium distribution.[3-5] We propose that these recent studies may help further reveal the underlying principles of biological clocks, and pave the way to exploit synthetic oscillators for switching and signalling functions. 1. Wagner et al. J. Phys. Chem. Lett. 2015, 6, 60. 2. Gurevich et al. Chem. Commun. 2015, 51, 5672. 3. Mukherjee et al. Angew. Chem. Int. Ed. 2015, 54, 12452. 4. Wagner et al. ChemPhysChem 2017, 18, 1842. 5. Maity et al. Nature Commun. 2019, 11, 681.

Resume : The current state of the art in artificial cell science relies on the construction of lipid vesicle membranes whose inherent properties, however, limit their applications particularly in sustaining cell internal biochemistry and communication between neighbors. Polymersomes are considered as ideal alternatives to liposomes because of their enhanced stability, chemical versatility, chemical and mechanical resistance. Nevertheless, the use of polymeric vesicles is restricted due to their low membrane permeability. Here, a suite of porous polymer membranes which is intrinsically permeable to molecules of defined sizes is explored as chassis for artificial cell, with the ideal functionalities of retaining specific molecules (e.g. protein and DNA) but allowing influx and efflux of small molecules (e.g. metabolites, signal molecules and mRNA). The porous vesicles are expected to form directly by self-assembly of copolymers, and the porosity is hypothesized to be controlled by varying experimental parameters during extrusion. The combinations of copolymers involve the mixtures of diblock copolymer PEG-PBD and triblock copolymer PEG-PPO-PEG with different molar ratios, and the solutions of two or more triblock copolymers PEO-PPO-PEO with different head-to-tail ratios. The porous polymer vesicle is novel in artificial cell science; thus, many potential applications can be tapped into, including for spatially-segregated biochemical reactions in polymer-based synthetic organelles.

Resume : High-performance photothermal agents remain highly required for realizing efficient tumor photoelimination. However, low-photoconversion and non-biodegradability of photothermal materials seriously lead to restricted tumor suppression or unavoidable biosafety issues. In such, a major mission is focused on developing efficient and dependable agents with prominent photothermal conversion efficiency for maximized cancer photoelimination. Herein, we developed a biodegradable photothermal therapeutic (PTT) agent, π-conjugated oligomer nanoparticles (F8-PEG NPs), for highly efficient cancer theranostics. By exploiting an oligomer with excellent near-infrared (NIR) absorption, the nanoparticles show a high photothermal conversion efficiency (PCE) up to 82% surpassing those of reported inorganic and organic PTT agents. In addition, the oligomer nanoparticles show excellent photostability on one hand but also good biodegradability. The F8-PEG NPs are also demonstrated to have excellent biosafety and PTT efficacy both in vitro and in vivo. This contribution not only proposes a promising oligomer-based PTT agent, but also provides insight into developing highly efficient nanomaterials for cancer theranostics.

Resume : Exploitation of new photosensitizes with sufficient oxygen-independent O2−• generation is highly desirable for overcoming hypoxia in photodynamic therapy (PDT). Herein, we report the first demonstration using a radical molecule as a new photosensitizer for hypoxic-overcoming photodynamic therapy. After self-assembling the radical molecules into nanoparticles (NPs), the NPs show good water dispersibility, good biocompatibility, board near infrared (NIR) absorption and emission at ~ 800 nm. Significantly, radical NPs remain stable in various biological solution, 100-days exposure to ambient environment, and long-term laser irradiation, which are ultrastable compared to many reported radical materials. Efficient 1O2 and O2−• generation and cytotoxicity were observed upon NIR irradiation. More importantly, even under hypoxia condition, sufficient oxygen-independent O2−• generation and cytotoxicity were observed addressing the most important hurdle for successful PDT in oxygen-deficient tumor microenvironment. This work demonstrates that stable radical molecules could have interesting properties suitable for novel biomedical applications.

Resume : Rational manipulation of energy utilization from excited-state radiation of theranostic agents with donor-acceptor structure is relatively unexplored. Herein, we present an effective strategy to tune the exciton dynamics of radiative excited state decay for augmenting two-photon nanotheranostics. As a proof of concept, two thermally activated delayed fluorescence (TADF) molecules with different electron-donating segments are engineered, which possess donor-acceptor structures and strong emissions in the deep-red region with aggregation-induced emission characteristics. Molecular simulations demonstrate that change of the electron-donating sections could effectively regulate the singlet-triplet energy gap and oscillator strength, which promises efficient energy flow. Two-photon laser with great permeability is used to excite TADF NPs to perform as theranostic agents with singlet oxygen generation and fluorescent imaging. These unique performances enable the proposed TADF emitters to exhibit tailored balances between two-photon singlet oxygen generation and fluorescence emission. This result demonstrates that TADF emitters can be rationally designed as superior candidates for nanotheranostics agents by the custom controlling exciton dynamics.

Resume : Sheet-like structures such as nanoflake and nanolamellae are of great interest in biomedical engineering, because the sharp edge or large surface area can affect the bacterial and cellular behaviors on attaching to these structures. The nanolamellar arrays can be readily constructed on the surface of polyetheretherketone (PEEK) through one-step plasma treatment, showing a re-crystallization and time-dependent growth process. The gap, thickness and size of the nanolamellar array are controlled by adjusting the volume of plasma injection and the treatment time, which in turn affect the antibacterial activity and the growth of osteoblasts. The sharp edge and dimensional parameters of the nanolamellar arrays contribute to the antibacterial activity. However, due to the large size of the osteoblast and the stiffness of the cell membrane, the osteoblasts can grow on the arrays, which is affected by the dimension of the arrays. The improved osteoblast proliferation also renders it desirable osteointegration activity. The overall results in this work offer insights into the antibacterial behavior and the osteogenesis of the nanolamellar arrays, thus assuring this type of structure better application in biomedical engineering.

Resume : Human adipose-derived stem cells (hASCs) can differentiate into multiple lineages and be harvested abundantly. However, the expression of pluripotency markers, which is important for the renewal and differentiation capabilities of hASCs, decreases during monolayer culture. Increasing evidence has proven that cells aggregated to form cell spheroids in 3D cell cultures better mimic the in vivo microenvironment and can enhance the expression of stemness markers. In this study, first, uniform hASC spheroids were formed by seeding cells in agarose microwell plates, and the size of the spheroids could be adjusted. Most importantly, the stemness expression of the spheroids increased significantly. Additionally, we utilized microbial transglutaminase (mTG), which is an enzyme that exhibits highly specific activity over a wide range of temperature and pH, to crosslink gelatin. The enzymatic crosslinking reaction is milder than physical and chemical methods, which may lead to cell death. The properties of the gelatin/mTG hydrogel were evaluated in detail. In addition, the spheroids were encapsulated in the 3D hydrogel successfully. The results showed that the hydrogel has low toxicity to the cells, which significantly proliferated in the 3D hydrogel. Moreover, the analysis of the differentiation potential indicated that the cell spheroids in the 3D hydrogel exhibited good activity, especially adipogenesis and chondrogenesis, compared to the cell suspension group. Furthermore, the in vivo data confirmed the excellent injectability and biocompatibility of the 3D hydrogel. Second, we demonstrated that cell spheroids entrapped in gelatin hydrogel can accelerate wound healing. To evaluate the in vivo effects of these spheroids/hydrogel system, we applied hASC single cells/hydrogel and hASC spheroids/hydrogel in a designed rat skin repair model. Results showed that skin wounds treated with hASC spheroids hydrogel system had faster-wound closure and a significantly higher ratio of angiogenesis. Based on the in vitro and in vivo results, the self‐assembled hASC spheroids hydrogel system may be a promising cellular source for skin tissue engineering and wound regeneration.

Resume : Multifunctional anti-reflective (AR) SiO2 nano-rod structures were fabricated on glass on an ITO substrate using nano-spheres in a hexagonal-closed-packing array in an attempt to improve the efficiency of light extraction. Compared to the reflection of flat ITO/glass substrates, surface reflection of AR patterned ITO/glass decreases with gradual change of refractive index, resulting in an increase in the amount of transmitted light. SiO2 nano rod structures were fabricated by a combination of polystyrene (PS)-based nano-sphere lithography (NSL) and reactive ion etching (RIE). Dimensions of height and diameter can be adjusted by selective gas etching process. O2, CHF3, and Ar gas were selected to fabricate the SiO2 nano structure. Finally, moth-eye patterned AR SiO2 nano structures were fabricated. The measurement results for our nanostructure (diameter: 150 nm, height: 400 nm) showed a 2% reflectance reduction in the 380~780 nm range compared to reflectance of flat ITO/glass substrate. Due to the deposition of SiO2 layer by Plasma Enhanced Chemical Vapor Deposition (PECVD), super hydrophilic nano patterns were obtained. To obtain an anti-fogging effect, we performed self-assembled monolayers (SAMs) treatment by applying perfluoro siloxane (PFS) on AR patterned SiO2 nanostructure. A field emission scanning electron microscope (FE-SEM) was used to investigate the morphology of the AR-patterned SiO2 nanostructure. Hydrophobicity was measured by contact angle measurement.

Resume : Fungal infections caused by Candida albicans have significantly increased through the formation of biofilm on living tissues and indwelling medical devices. These infections have huge clinical implications since fungal biofilm displays increased resistance to antifungal agents, therefore, it shows significant risk to immunocompromised patients.1 Morbidity and health care costs related to fungal infections has become a serious medical problem. Traditional treatments for Candida infections are associated with drugs that show high toxicity and antimicrobial resistance. Developing new antimicrobial agents to disrupt fungal biofilm has become an urgent need in the current scenario. The booming development of water-soluble conjugated polymers in the past decades2,3 has shown promising effects against bacteria. In this context, water-soluble conjugated polymers functionalized with benzimidazolium groups were synthesized by Sonogashira coupling, and antimicrobial properties against Candida albicans were studied. The conjugated polymers differ by the nature of the backbone such as polyfluorene(PF-PPE), poly(para-phenylene ethynylene)(p-Benzimi-PPE), poly(meta-phenylene ethynylene)(m-Benzimi-PPE). The photophysical properties of the polymers have systematically investigated.4 PF-PPE display absorption maximum at 380 nm and emission maximum at 475 nm, fluorescence quantum yield is φH2O=0.05, φMeOH=0.098. The antimicrobial activities of the three main chain types of conjugated polymers irradiated at visible light 420 nm which decreased in the order: PF-PPE > p-Benzimi-PPE > m-Benzimi-PPE. Under visible light irradiation, the PF-PPE showed pronounced antifungal properties against Candida albicans under all three modalities (planktonic, biofilm inhibition and biofilm eradication.

Resume : One great challenge for bio-sensing is to ensure that detection/transduction of biochemically rich systems is fully mastered to reliably record relevant information descriptors. For neuro-sensing with microelectrode arrays (MEAs), signal transduction lies at the interface between extracellular ionic currents and the electrodes. By chemically/morphologically engineering electrode materials’ interface to ensure the best electrochemical surface impedance, the aim is to find the right materials that detect ionic signals from neurons and transduce them into electronic signals with the lowest information loss. In this direction, we show how to lower the surface impedance of microelectrodes by electropolymerization of synthesized thiophene-based monomers, functionalized for higher cell biocompatibility and higher electrochemical performances. By in-situ monitoring of impedance change with voltage-ramped impedance spectroscopy, we systematically screened electrical and chemical deposition conditions to control the materials’ morphology (confirmed by atomic force and electron microscopy) reaching lower impedances than commercial MEAs and comparable to state-of-the art spin-coated polymers. With the presented preliminary biocompatibility tests, we aim to show that unconventional deposition processes can access to wider ranges of materials’ chemistry and morphology that cope with biological-constraints/electrical-performances to unlock future emerging bioelectronics technologies.

Resume : According to the WHO, Malaria is one of the most severe infectious diseases in the world, affecting almost half of the population. Thus, early diagnosis becomes critical. This disease is caused by the Plasmodium parasite whose main human-infective species are: P. Falciparum (Pf), P. Vivax (Pv), P. Ovale (Po), P. Knowlesi (Pk) and P. Malariae (Pm). Point-of-Care (PoC) systems promise to be a fast and costless alternative to current diagnosis methods, suitable for resource limited settings. Nevertheless, they still present some limitations such as low detection limit or the need of expensive optical equipment. More importantly, most of these PoC systems only focus on the detection of pan-Plasmodium, or Pf, leaving infections caused by other species undiagnosed. Increasing infections of Pv, Pk or Po in countries such as India or Malaysia have been recently reported, urging the development of new PoC devices for their detection. In previous work we have shown a novel Lab-on-a-Chip (LoC) electrochemical biosensor based on real-time LAMP and Ion-Sensitive Field Electrode transistors (ISFET) able to detect Pf. In this work, we propose to extend this system to the detection of other Plasmodium species. This methodology allow us to combine the accuracy of nucleic acid amplification with sensitive and unlabeled detection provided by the ISFET sensors. Furthermore, this LoC technology is promising for multiplexing, allowing the detection of several pathogens at once, ideal for PoC applications.

Resume : The preventive and personalized medicine strategy for disease treatment stands apart from traditional medicine therapy. Nowadays, non-invasive monitoring and diagnostic systems based on wearable electronics and e-skin are considered as crucially important for implementation of smart healthcare technologies. However, materials for such devices should fulfill specific requirements, e.g. have a good combination of charge-transport properties, mechanical flexibility, and biocompatibility. In this work, we explored the biological effects of a series of different organic semiconductors on in vitro living system. Human embryo lung fibroblasts were incubated at standard conditions with thin films of studied materials. Cells were fixed at different time points in order to find out acute and long-term effects on fibroblasts (30 hours, 96 hours, 14 days). Flow cytometry and immunofluorescence microscopy techniques were performed with antibodies to H2A histone family member X and 8-oxoguanine for DNA damages evaluation. The occurred changes in cell metabolism were detected by real-time polymerase chain reaction, which was carried out with primers to the genes involved in apoptosis regulation and oxidative stress in cells. Results of our study demonstrated that some of the studied organic semiconductors represent biocompatible materials suitable for wearableand on-skin electronics.

Resume : Water scarcity is a large global challenge threatening approximately four billion people. Ambient air contains 13000 trillion liters of water vapor equivalent to approximately 10% of all freshwater in all the world lakes. It can serve as an alternative water resource for addressing the water crisis. Some materials can be used to extract water from the atmosphere, but they need either an expensive water collection device or high temperature to achieve water vapor desorption, which are both costly and labor intensive. The objective is to develop a material that can be used to harvest water from the air in a cost and energy efficient manner. Superabsorbent polymers (SAPs) that have water uptake capacity of 200 to 500 times of their own weight of liquid water have not been investigated for moisture harvesting. Herein, inspired by desert beetles and cactus plants, we investigated the efficacy of SAPs, sponges coated with PNIPAAM cones to sorb water vapor at relative humidity from 30 to 90%, as commonly found in ambient atmospheric conditions. A state-of-the-art Dynamic Vapor Sorption was used to evaluate the kinetics and diffusion properties of water vapor at a relative humidity of 30 to 90% and temperatures of 10 to 50°C. The kinetics of moisture uptake will be also investigated for various humidified airflow rates. The kinetics and diffusion properties of the SAPs will then be quantified using physics-based models.

Resume : Cellular signalling through diffusible factors and direct cell-to-cell contacts are known to play a critical role in controlling cell viability. To understand how mechanical neuron-neuron contact affects neural survival is essential for study brain development. However, tools to systematically manipulate inter-neuron connection rarely occurs in previous studies. Herein, we developed a strategy to impose stereotypic interneuronal spacing and connectivity using topology micropatterns. With the artificial surface, we found that increased inter-neuron connectivity promotes the survival of neurons by activating neuron survival pathways. Overall, our approach helped to pave the way to improve primary neuron cell culture methodology, and more importantly, enable us to manipulate neuronal survival simply by controlling the connectivity between neurons.

Resume : The 3-dimensional(3D) porous materials or scaffold have been widely applied to the different fields. Here, we report an innovative manufacturing process for the fabrication of 3D porous structures containing any ingredients even the living cells via the chemical vapor deposition (CVD). This report indicates that the scaffold via sublimation/deposition process could encapsulate any substances, including living cells, growth factors and functional guiding molecules, to form a mono- or multi-functional scaffold and performed its biological function. According to the results, the survival rate of the cell-loaded scaffold via sublimation/deposition process was 80.8±5.3%. The proliferation and osteogenesis activities of MC3T3-E1 loaded in scaffold composited with ingredients, fibroblast growth factor (FGF-2) and bone morphogenetic protein (BMP-2), respectively, could be enhanced, comparing with cell-loaded scaffold without ingredients. Otherwise, osteogenesis and adipogenesis of human adipose-derived stem cells (hASCs) encapsulated in scaffold composited with PRP and cultured with induction medium performed better than the others group without PRP or induction medium. Moreover, according to the neurogenesis test, neurite length of pheochromocytoma 12 cell line (PC12) loaded in scaffold composited with ingredients, PEDOT:PSS and PRP, was 115.3 ± 26.8 μm which is the longest in different groups and tendency of neurogenesis activity were also as same as neurite length. Based on these result, the ingredients could be successfully loaded in the same Trojan scaffold, and also perform their individual functions. This novel approach and scaffold mentioned here provide another way for fabricating multifunctional scaffold with potentially broad applicability.

Resume : Upconversion nanoparticles (UCNPs) are commonly used as energy donor via a LRET (luminescence resonance energy transfer) in biological applications. In contrast to classic RET donors such as gold nanoparticles, quantum dots, UCNPs can emit near-infrared (NIR) upon the NIR excitation, which provides reduced signal-to-noise ratio due to the strong penetration and less autofluorescence in NIR region called diagnostic window. Here, we report NIR-to-NIR signal based LRET system for detection of progesterone, a natural steroid female sex hormone. We synthesized NaYF4@NaYF4:Yb,Tm@NaYF4 inert-core/active-shell/inert-shell UCNPs as LRET donor. Progesterone-HRP-IRdye and progesterone-BSA-IRdye were used as LRET acceptors with different size for efficient LRET from the UCNPs due to exact spectrum match of the UCNP’s emission and IRdye QC-1’s absorption. Anti-progesterone antibody was conjugated on the surface of water-soluble UCNPs. Progesterone was detected in NIR-to-NIR signal based LRET system via competitive immunoassay. The limitation of detection for progesterone was determined to be 1.36 pg/ml in 10-fold diluted human serum samples. We believe that the LRET system have considerable diagnostic potential, being background-free and able to rapidly detect biomarkers.

Resume : Local mechanical cues can affect crucial fate decisions of living cells. Transepithelial stress has been discussed in the context of epithelial monolayers, but the lack of appropriate experimental systems led current studies to approximate it simply as an in-plane stress. To evaluate possible contribution of force vectors acting in other directions, we reconstituted double epithelium in a 3D-printed GeminiChip containing a sessile and a pendant channel. Intriguingly, the sessile epithelia were prone to apoptotic cell extrusion upon crowding, whereas the pendant counterpart favored live cell delamination. Transcriptome analyses showed upregulation of RhoA, BMP2 and hypoxia signaling genes in the pendant epithelium, consistent with the onset of an epithelial-mesenchymal transition program. HepG2 microtumor spheroids also displayed differential spreading patterns in the sessile and pendant configuration. Using multilayered GeminiChip, our results uncover a progressive yet critical role of perpendicular force vectors in collective cell behaviors and point at fundamental importance of these forces in the biology of cancer.

Resume : Biological processes such as morphogenesis, angiogenesis or embryogenesis involves group of cells coordinating their movements collectively to achieve specific functions, in a constricted fashion. Unlike single cell, collective cellular motions, which involve intercellular coordination, are much more complex and largely remain mysterious. Variances in environment could easily lead to changes in cell behaviors; factors such as chemical, physical or mechanical signals are common regulators in guiding cell migration. Among these factors, topological cue is a critical, yet easily neglected factor. Different from most benchside scenarios, in which migrations are allowed on infinite surfaces, the physiological microenvironment of cellular migration is usually confined. Here we built fibronectin patterns on polyacrylamide substrate to study confined cell migration. We showed that motion of cell cohort could be modeled through topological cues and confinement. Madin-Darby Canine Kidney (MDCK) cell line is used as an epithelial model to describe a form of oscillation phenomenon under various circular confinement, which amplitude and frequency vary with both the size of constrain as well as regions in the confined monolayer. Through spatio-temporal force analysis, increased intercellular tension and cell-substrate traction are observed with increasing degree of confinement. Together with confocal microscopy of actin cytoskeleton and average orientation field mapping on the cell sheet, a possible fluid-to-solid transition could attribute to this interesting collective cell motion.

Resume : Conventional drug-eluting stents (DESs), biomedical implants, mainly use polymers or laser etching to load drugs. However, there are limitations in that polymers cause side effects such as late-thrombosis in the body and laser etching is complicated and expensive. Herein, we propose a porous nanostructured silica film for polymer-free DESs platform, which is synthesized by a sol-gel process using a catalyst, a silicon source, and structure-directing agents. As the structure-directing agents form micelles and grow on the surface, the porous nanostructured silica film is formed and has tunable pore sizes and channel lengths by adjusting reagents, molar ratios and reaction time. This suggests that a large amount of materials can be loaded, from large molecular weight molecules to small ones, and the films can be easily formed on the surface of commercial bare-metal stent. In addition, it is expected to be physically stable in the actual applications through pico-indentation experiment, expansion simulation and SEM, which evaluates the physical characteristics such as young's modulus (85.26 GPa) and hardness (2.69 GPa). Moreover, surface functionalization into hydrophobic with silane coupling agents (Octyltrimethoxysilane, Hexadecyltrimethoxysilane) allow the hydrophobic drugs to be loaded without polymers. The porous nanostructured silica film may represent an attractive platform that can be used in many other areas as well as polymer-free DESs.

Resume : Bionanocomposite films based of polycaprolactone (PCL) and fish collagen nanoparticles embedded with sea buckthorn oil were prepared by the solvent evaporation method at room temperature conditions. These materials were performed in order to be used as promising candidates in medical applications like regeneration of skin wounds and not only (surgical suture and prosthetic devices) by improvement the proliferation of fibroblast cells properties. The following raw materials were used for obtaining the polymeric composites: polycaprolactone (Sigma-Aldrich, Mw = 45,000); fish collagen extracted in the laboratory from fish waste; pure cyclohexanone (Sigma-Aldrich); acetic acid (Sigma-Aldrich) and sea buckthorn oil. Both polymeric films developed as well as collagen and sea buckthorn oil respectively have been physico-chemically and biologically characterized (FT-IR, SEM, UV-vis, EDX, HPLC, SDS–PAGE, WCA/water contact angle and fibroblast cell cultures study). Experimental results suggest that polycaprolactone films with collagen and sea buckthorn could be used for medical applications, when additional studies are required. Keywords: polymeric composites, skin wounds, fibroblast cell cultures ACKNOWLEDGEMENTS The work of PETRUTA PREDA has been funded by the Operational Programme Human Capital of the Ministry of European Funds through the Financial Agreement 51668/09.07.2019, SMIS code 124705. This work was supported by the grant COP A 1.2.3., ID: P_40_197/2016.

Resume : The study of a composite system made of semi-flexible polymeric networks combined with colloidal particles has remained in its infancy despite its ubiquitous nature in the biological space. By imparting functionalities into colloids or polymer networks, reconfigurable and active materials system that dynamically respond to external stimuli can be realized. Here, we demonstrate the 3D hydrogel composites consisting of semi-flexible fibrin networks and colloids. We develop the methods of integration of colloidal particles into fibrin networks and observe the structure of the resulting composite hydrogels. We characterize the mechanical properties by measuring oscillatory shear elastic moduli at the linear and non-linear regimes. The relation between the structure and the mechanical properties are discussed. Furthermore, we synthesize thermo-responsive hard-sphere colloids and soft-microgel colloids via atom-transfer-radical-polymerization and surfactant-free emulsion polymerization respectively. We successfully incorporate these into fibrin networks using the developed method. The changes in structure and dynamics upon the temperature change are observed and the origin of this switchable property is discussed.

Resume : In the last few years, Ceria (CeO2) nanostructures are thought to improve the biointerface mechanical properties, but also to stimulate the regenerating tissue biochemical activity by neutralizing the oxidative stress and stimulating cells proliferation. Nevertheless, there is a lack of information of mamallian cells on Ceria coatings, especially with well-defined nano and microstructured surface. Within this context, we present for the first time new designed pyramid shaped nanostructured ceria films obtained by Pulsed Laser Deposition (PLD), targeting the modulated response of SaOs-2 bone cells. The nanostructured surfaces obtained by PLD revealed shapes from the quasipyramidal, with rounded edges and dimensions of 90-120 nm, to the sharp edges and dimensions up to 350 nm, obtained by varying the number of pulses. The shapes and sizes of the nanostructures influenced both wettability and cellular behaviour. Nevertheless, the influence of pyramidal shaped ceria on the in vitro biological performance of SaOs-2 cells used as bone cell model was demonstrated by the differences in early adhesion and distribution of phenotype SaOs-2 cells, onto the ceria surface. In conclusion, different nanostructured ceria films obtained by PLD influenced especially the early response of osteosarcoma cell and are good candidates to improve the performance of orthopedic implants. In perspective, different cells lines response will be analysed toward establishing an osteogenic response. Acknowledgement This work was supported by the National Authority for Research and Innovation in the frame of the Nucleus Program and grants of the Romanian Ministry of Research and Innovation,CCCDI-UEFISCDI, project numbers PN-III-P1-1.2-PCCDI-2017- 0637 (MultiMonD2).

Resume : The characterization of the protein amino-acids in natural cells and mimetic medias is one of great value in the amino-acid studies. Using results of investigations for intermolecular interaction between the C60 and ds-, ss- DNA sequences [1], predictive modeling of a interface structures for the fullerol (immobilized by –OH groups fullerene C60) molecules in a cluster and this molecule at an interface with metal ion (Cu or Ag ) complex having coordinative bond to selected amino-acid (glycine, alanine, methionine, histidine) molecules [2,3] has been realized. This modeling should derive interface properties from the chemical functionalities of the constituents, while operating stimuli- response molecular nanostructures in aqueous solutions with amino-acid molecules. Modeling was carried out taking in account that these interfaces organization may increase the photoactivity and the biocompatibility to this carbon molecule counterpart. The interface designing concept as the base for the fullerol molecule in a cluster sensor and molecular ion metal complex sensor development has been discussed. Based on well established rationale of interface organization in biological macromolecules (nucleic acids, proteins), driven by non-covalent interactions (hydrogen bonding, hydrophobic effect and electrostatic interaction) in living cells, we have plan to select biomolecules for non-covalent interaction with a core of the fullerol molecule and a molecule of organic ligand in ion metal complex – amino acids. Then molecular interface organization in solutions can be revealed by photospectroscopy. From experimental results specific interface formation between [Сuх(5-amtetrazole)у]2 complex and histidine molecule for organic specially synthesis ligand with the same coordination nature of this amino-acid molecule has been determined. A special structure of a ligand and histidine molecules gives more coordination geometry to molecular complexes, determines specific interface formation in this supramolecule.Selective coordination of such supramolecule in solutions with the histidine molecules (pH 2.7 – 12.9) was confirmed by absorbance spectra with the intensive band (600 800 nm) and it is assigned to the d – d transition of Cu. Maximum position shifted from 753 to 615 nm after adding the histidine was demonstrated. The histidine concentration effect for the solutions with the fullerol molecular clusters and the functionalized by Cu –azole ligand complex fullerol molecules was also determined. The next step is the development of controlled by light excitation interface between the fullerol, selected ion metal complex and many protein-acid molecules organization for their photo-spectroscopy recognition and single molecular biosensor controlled design. References: 1. O. Kysil, I.Sporysh, E.Buzaneva, T. Erb, G.Gobsch, U.Ritter, P.Scharff, Mat. Sc. and Eng. B169/1-3 (2010) 85. 2. O. A. Bondar, L. V. Lukashuk, A. B. Lysenko, H. Krautscheid, E. B. Rusanov, A. N. Chernega, K V. Domasevitch, Cryst. Eng. Comm, 10 (2008), 1216. 3. J. G. Mesu; T. Visser; F. Soulimani; E. E. van Faassen; P. de Peinder; A. M. Beale; B. M. Weckhuysen, Inorg. Chem., 45/5 (2006) 1960.

Resume : Antibiotic resistance is one of the most pressing problems of modern medical practice. This situation should be addressed through the rational and correct prescribing antimicrobial agents in clinics. Changes in Ukraine's health care system have the need for reconstruction and restoration of medical facilities. The use of ordinary repair materials for this purpose can not be used. Studies have shown the dependence of adhesive and colonization properties of clinical antibiotic-resistant strains of microorganisms from the effects of materials which based on TiO 2 Degussa P25 with photocatalytic activity under UV with a wavelength of 365 nm with a different exposure time. The experiment was carried out by the method of diffusion, a microorganism lawn culture was sown on a cup with a nutrient medium, a part of the cup was covered with a light-proof material, and placed in a light chamber (the duration of irradiation of the lawn was different) . After 24 hours cultivation of lawn cultures of antibiotic-resistant strains of microorganisms were recorded. Established that material with nano-TiO 2 under UV irradiation him with a wavelength of 365 nm resulted in stunted growth and development of culture lawn clinical strain of microorganism. Thus, from a culture with a microbial load of 10^5 cells / ml on the control samples developed a dense lawn, indicating the regeneration of the culture, its adhesion to the surface and colonization of the surface. Nano-TiO 2 at UV with a wavelength of 365 nm caused a delay in the development of all cultures of clinical strains of microorganisms. Thus, from the working suspension with a microbial load of 10^5 cells / ml grew single colonies in an amount of from 2 to 4 CFU. Materials based on Degussa P25 TiO 2 are promising for the manufacture of surfaces of medical equipment where there is a threat of colonization by antibiotic resistant strains of microorganisms.

Resume : Cisplatin (cis-Pt) is a complex of platinum which widely used as an anticancer drug. Transplatin (trans-Pt) has the same chemical formula, but different positions of atoms. Cisplatin connects to DNA in cancer cells and stops DNA replication, namely making cross-links between guanine bases. Transplatin is less reactive to DNA but also demonstrate cytotoxicity effect. In this work we make an attempt to connect the differences in the biological activity of mentioned structures with the data obtained by optical spectroscopy methods. The UV-vis spectra as well as fluorescence and phosphorescence spectra of water solutions of cis-Pt and trans-Pt were investigated at temperatures 300 and 77 K. Quantum chemical calculations were used for correct interpretation of obtained results. We also characterized these compounds using such powerful method as Raman spectroscopy.

Resume : To date, the therapeutic properties of π-conjugated polymers especially in the form of aqueous nanoparticles, the so-called conjugated polymer nanoparticles (CPNs), have been verified merely upon laser irradiation via the well-established photodynamic and photothermal therapies. In this contribution, it is manifested for the first time the natural anticancer properties of single CPNs. This has been accomplished by studying the cell viability of new CPNs in physiological human umbilical cord mesenchymal stem cells (WJ-MSC), human colorectal carcinoma cell line (HCT116) and metastatic human melanoma cell line (WM164). The discovery of natural anticancer properties in conjugated polymers can form a new frontier in nano-biotechnology and nanomedicine and represent a new direction that is orthogonal to the more established areas of conjugated polymers for optoelectronic devices and conjugated polyelectrolyte biosensors. The combined natural anticancer and bioimaging properties of CPNs point to a new strategy for obtaining novel organic nanomaterials for cancer theranostics.

Resume : Low-bandgap aqueous conjugated polymer nanoparticles (CPNs) have been prepared and applied in biological applications, especially in bio-imaging, due to their unique optoelectronic properties.In this study, we successfully synthesized a series of conjugated polymers combining thiophene as the electron donating and quinoxaline as the electron deficient (TQs) with varying the number of fluoro atoms in the repeat unit. Water-soluble nanoparticles formatted by two different methods (nanoprecipitation and encapsulation), supporting their potential use as low-bandgap fluorescent probes for bio-imaging.The DLS measurements indicate that all CPNs in aqueous suspension have a unimodal size distribution less than 80nm.TEM & SEM measurements showed that the CPNs have spherical shape.The optical properties of the CPNs show light absorption and fluorescence emission in the UV-Vis region,tunable depending on the structure, the position and the number of fluoro atoms on the polymer backbone.It is revealed a significant reduction of the fluorescence quantum yield in aqueous media derived from severe aggregation and charge transfer induced fluorescence quenching, which can be controlled with proper rational design on the polymer backbone. Moreover, the on-going tests for cellular cytotoxicity and the ability of the obtained probes to image cancer cells are of great importance.Overall, CP dots introduce a new generation of fluorescent probes that appear to be the quintessential contrast agents

Resume : Long-term use of ocular prostheses causes frequent ocular infections with a number of adverse effects.The antibacterial and antifungal activity was investigated of Ag-doped Al2O3 nanolayers deposited by radioactive magnetron sputtering on ocular prostheses after a two-year period. A microbiological study was performed to determine the antibacterial action of the nanocomposite Ag/Al2O3 nanolayers against gram positive and gram negative bacteria, and an antifungal action against Candida albicans. From the conducted microbiological studies we have found the preservation of the antibacterial and antifungal action of the Ag/Al2O3 nanocoating of the eye prostheses after two years. The results of microbiological studies show that antibacterial and antifungal activity has the same full inactivation by intensity for the reference period. Experimental studies show a very promising application of such antibacterial and antifungal Ag/Al2O3 nanocoating to reduce ocular infections in the placement of ocular prostheses over a prolonged period of use. Keywords: Ag/Al2O3 nanolayers, antibacterial and antifungal action, ocular prostheses coating, two-year period

Resume : Nanoparticles mediated drug delivery system has immense therapeutic applications especially in the field of cancer treatment. The chemo-therapeutic efficacy is enhanced when combined with radiation therapy or thermal therapy (Hyperthermia). For thermalchemotherapy, appropriate functionalised magnetic nanoparticles with desired magnetic parameter are pivotal. In this direction, we synthesised a highly aqueous dispersible PEG-dicarboxylic acid functionalised iron oxide (Fe3O4) nanocluster with superior magnetic properties by a simple solvothermal approach. The well distributed nanocluster (size~200nm) are formed by the assembly of smaller nanoparticles. Fe3O4 crystallizes in inverse spinel structure with crystallite size of 16.9 nm and possess mesoporous structure with high specific surface area of 71.3 m²/g. The carboxyl group was activated using hydrazine hydrate to form pH sensitive hydrazone bond which further was utilised to attach with doxorubicin (DOX) through C=O linkage. High drug loading efficacy was achieved due mesoporous nature of the nanoparticles and carboxyl group activation. This system shows higher and sustained release at pH 4.3 in comparison to normal physiological pH of 7.4 because of labile hydrazone bond. The synthesised Fe3O4 nanoclusters are biocompatible upto a concentration of 1mg as observed in vitro in MCF-7 breast cancer cell line. Due to higher saturation magnetisation of the nanocluster, a hyperthermic temperature of ~ 43 ºC was achieved in just 105 s at nanoparticle concentration of 2 mg/ml and at the applied AC magnetic field strength of 35.2 kA/m and frequency of 316 kHz. Hence, the PEGylated mesoporous Fe3O4 nanoclusters can be effectively utilised for thermochemotherapy of cancer.

Resume : 3D bioprinting is a widely used technology to dispense cell-laden biomaterials for rapid fabrication of complex 3D tissue constructs or artificial organs. To date, many studies have been investigated the deposition and patterning of cell-laden bioinks with a 3D bioprinter. However, the precise positioning, reasonable mechanical properties, and controlled cell distributions of constructs in 3D bioprinting system still remain technical challenges. In this study, we developed heterogeneous cell-laden microchannel network using human umbilical vein endothelial cell-cardiomyocytes by a direct patterning with a 3D bioprinter. We fabricated 3D tissue constructs consisting of the core (human umbilical vein endothelial cell -laden collagen) and the sheath (cardiomyocytes-laden gelatin methacrylate). We could achieve a stable 3D multilayered core-sheath structure with the reasonable elastic modulus. This system also facilitated cell alignment and migration within each constructs and promoted vascular network with high cell viability. Calcium imaging was used to optically probe intracellular calcium ion signals during excitation-contraction coupling in cardiomyocytes within 3D vascular network. This paper presents the new approach for fabricating vascularized heterogeneous 3D scaffolds and highly controlled deposition technique of bioinks. The cell-laden 3D constructs could be extended to serve as in vitro models for clinical cardiovascular disease researches and cardiovascular tissue regenerations.

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

Resume : Gold nanorods (AuNRs) are successfully employed in drug delivery, biosensors, and biotechnologies [1,2]. Their wide success is due to their unique chemical properties, biocompatibility, easy, cheap and versatile synthesis. In this framework, hydropilic AuNRs were synthetized with the aim to obtain strongly hydrophilic nanomaterials, suitable for drug delivery. AuNRs were investigated by UV-Vis-NIR, FT-IR and HR-XPS spectrocopies, confirming nanosize, with typical surface plasmon resonance (SPR) bands at 550 nm and 900 nm, and surface functionalization by ascorbic acid (AA) and cetyl trimethyl ammonium bromide (CTAB). Therefore, AuNRs were used as drug delivery system for copper (I)-based anti-tumor complex namely [Cu(PTA)4]+[BF4]- (PTA = 1,3,5-triaza-7-phosphadamantane) [3-5]. The loading procedures and efficiency of Cu(I) complexes on the AuNRs surface were optimized in order to control their bioavailability and release. References [1] Park K., Drummy L. F., Wadams R. C., Koerner H., Nepal D., Fabris L., Vaia R. A. Growth Mechanism of Gold Nanorods. Chem. Mater. 2013; 25: 555-563 [2] Venditti I. Engineered gold-based nanomaterials: morphologies and functionalities in biomedical applications. A mini review. Bioengineering. 2019; 6(2): 53 [3] Gandin V., Tisato F., Dolmella A., Pellei M., Santini C., Giorgetti M., Marzano C., Porchia M. In Vitro and in Vivo Anticancer Activity of Copper(I) Complexes with Homoscorpionate Tridentate Tris(pyrazolyl)borate and Auxiliary Monodentate Phosphine Ligands. J. Med. Chem. 2014, 57 (11): 4745-4760. [4] M. Porchia, F. Benetollo, F. Refosco, F. Tisato, C. Marzano, V. Gandin. Synthesis and structural characterization of copper(I) complexes bearing N-methyl-1,3,5-triaza-7-phosphaadamantane (mPTA): Cytotoxic activity evaluation of a series of water soluble Cu(I) derivatives containing PTA, PTAH and mPTA ligands. J. Inorg. Biochem. 2009; 103 (12): 1644 [5] Fratoddi I., Venditti I., Battocchio C., Carlini L., Porchia M., Tisato F., Bondino F., Magnano E., Pellei M., Santini C. Highly hydrophilic gold nanoparticles as carrier for anticancer copper(I) complexes: loading and release studies for biomedical applications. Nanomaterials. 2019; 9: 772 Acknowledgements: The Grant of Excellence Departments, MIUR (ARTICOLO 1, COMMI 314 – 337 LEGGE 232/2016), is gratefully acknowledged by authors of Roma Tre University.

Resume : Copper complexes are coming out as metal-based drugs candidates for the treatment of cancer, due to their wide structural variability, biologically accessible redox properties and bioavailability. Recently, in our quest to find suitable ligands in the design of copper-based anticancer agents, we focused our attention on the synthesis of copper complexes of bis(azol-1-yl)carboxylate ligands functionalized with biomolecules. In addition, Cu(II) complexes of alkyl bis(pyrazol-1-yl)acetate ligands have been investigated for the development of a new and more efficient promoter for the Kharasch-Sosnovsky reaction to oxidize alkenes in allyl position. Since such coordination compounds have low solubility in aqueous medium, it is necessary to design a strategic approach allowing for drug delivery. By conjugating the copper complexes with hydrophilic gold nanoparticles, it is possible to improve their solubility and stability in water, increasing their bioavailability. Moreover, these drug delivery systems allow the investigation of a slow and controlled release of copper complexes [1]. In this context, we carried out a spectroscopic investigation of the molecular, electronic structure and coordination geometry of a selection of Cu(II)-coordination compounds, by means of complementary X-ray techniques induced by Synchrotron Radiation: the molecular and electronic structure were probed by means of SR-XPS and NEXAFS, the oxidation state and the local coordination chemistry of the metal ion were assessed by Cu K-edge XAFS analysed in the near edge (XANES) and extended (EXAFS) regions.

Resume : In this study, poly-L-dopa nanoparticle-based drug delivery system was designed for near-infrared light controlled trimodal therapy in which photodynamic therapy (PDT), photothermal therapy (PTT) and chemotherapy are combined to produce synergistic therapeutic effects. Poly-L-dopa nanoparticles (PLD NPs) were synthesized by oxidation and self-polymerization of L-DOPA with KMnO_4. For designing purposes of PTT, PLD NPs were modified with the photosensitizer, pheophorbide a (PheoA), via reducible disulfide linker for glutathione-responsive intracellular release. Due to the ability to convert NIR light into heat, PLD NPs could be used as a photothermal agent without further modification for PTT. Also, PLD NPs have a fluorescence resonance energy transfer- (FRET) based self-quenching effect which reduces the side effects by keeping the system photo-inactive during blood circulation. PheoA modified PLD NPs (PLD-PheoA NPs) were loaded with chemotherapy drug, doxorubicin (Dox), through ᴨ-ᴨ stacking and hydrogen bonding. The in vitro antitumor effect of PLD-PheoA/Dox NPs with trimodal PDT/PTT/chemotherapy was investigated in terms of photothermal efficiency, photoactivity, stimuli-responsive drug release, cellular uptake, and therapeutic efficacy. The best of our knowledge, this is the only study presented in literature, using poly-L-dopa nanoparticles with trimodal synergistic therapy approach for cancer treatment.

Resume : To make micropattern including bio-substances on nano-mesh, we developed the photo-crosslinking process using hydrogel. For in-situ micropatterning, the synthesized hyaluronic acid was empolyed with transparent micromold and UV irradiation. The photosensitive hyaluronic acid was rapidly cross-linked through the porous nano-mesh. When hyaluronic acid is patterned on the nanomesh, drugs and cells can be stably selected, and the release of drugs and the behavior of various cells can be controlled according to the patterning conditions. The immobilized material was released by diffusion, which was very precisely controlled through the coating of hyaluronic acid and nanomesh, and the theoretical verification with finite element analysis was performed. The proposed research could be used in the field of tissue engineering for local drug delivery or regeneration of damaged tissues in the body.

Resume : Connecting nanostructured materials to biological compartments is a crucial step in prosthetic applications, where the interfacing surfaces should provide minimal undesired perturbation to the target tissue. Ultimately, the (nano)material of choice has to be biocompatible and promote cellular growth and adhesion with minimal cytotoxicity or dis-regulation of, for example, cellular activity and proliferation. In this context, carbon nanomaterials, including nanotubes and graphene, are particularly well suited for the design and construction of functional interfaces. This is mainly due to the extraordinary properties of these novel materials, which combine mechanical strength, thermal and electrical conductivity. Our group has been involved in the organic functionalization of various types of nanocarbons, including carbon nanotubes and graphene. The organic functionalization offers the great advantage of producing soluble and easy-to-handle materials. As a consequence, since biocompatibility is expected to improve upon functionalization, many modified carbon nanomaterials may be useful in the field of nanomedicine. In particular, we have shown that carbon nanotubes can act as active substrates for neuronal growth, a field that has given so far very exciting results. Nanotubes are compatible with neurons, but, especially, they play a very interesting role in interneuronal communication. Improved synaptic communication is just one example. Research toward nerve regeneration in damaged tissues has also given very interesting results. During this talk, we will show the latest and most exciting results obtained in our laboratories in these fast developing fields.

Resume : Engineering of the surface is the multidisciplinary research of materials science and has a broad range of applications to chemistry, biology, engineering and medicine. Surface modification of a biomaterial can be done by different methods for altering into required characteristics, such as size, morphology, topology, wettability, roughness, surface charge, reactivity, biocompatibility and applicability. Tissue engineering is the use of a combination of cells, engineering and materials methods, and suitable biochemical and physicochemical factors to improve or replace biological functions of tissues. Here we provide an overview of the various applications of our surface modification systems and also discuss successes to date, current limitations and future directions. We developed surface modification system of nanotubes, nanoparticles, polymers, plastic wares, polydimethylsiloxane chips, using chemicals, zwitterionic polymers, polyethylene glycol (PEG), 3-aminopropyltriethoxysilane (APTES), extracellular matrix (ECM), other bioactive molecules, etc for efficiently enhancing cell functions. Our results highlight an innovative surface-modified biomaterials for advance cell culture and tissue regeneration system and may allow the development of enabling technologies for tissue engineering and regenerative medicine applications.

Resume : Exohedral van der Waals (vdW) hybrids comprising carbon nanotubes (CNT) and fullerene molecules (C60) may be used for engineering of carbon nano-materials with tunable physiochemical properties. As the hybrids preserve the sp2 hybridization of the components, superior electron transport, low percolation threshold, good electron accepting and efficient singlet oxygen sensitizing ability are expected. These hybrids may be useful as electron acceptors and charge carriers in bulk-heterojunction organic photovoltaics (OPV). In the reported study we demonstrate that induced SP3 point defects in CNT (via UV/O3 treatment) can be used for controlling the nano-structure of CNT- C60 hybrids. We describe a two-step process for assembly of CNTs networks and thermal (vacuum) sublimation of fullerenes nanocrystals. Transmission electron microscopy indicates that the hybrids comprise of random 3D scaffolds of individual CNT and fullerite nanocrystals, and Raman analysis reveals their non-covalent nature. While surface migration of the fullerenes on the CNT surface leads to coarsening of the nanocrystals, we find that controlled induction of SP3 point defects in the CNT can trap the initial nano-morphology and preserve the nano-dimensions and structure of the fullerene crystals, also at elevated temperatures and prolonged annealing. The nano-morphology of the treated nanotubes is preserved also when the hybrids are coated by a polymer layer (poly(3-hexylthiophene-2,5-diyl, P3HT), and the polymer-hybrid films show significant quenching of the photoluminescence, indicating that these hybrids could be useful in photovoltaic applications.

Resume : We demonstrate an ultrasensitive strain-gauge sensor using a conductive and flexible 3D graphene aerogel that enables detecting small pressures and various biological signals from the movement of human skin. The active element of the sensor is composed of a 3D graphene nanoporous framework made of graphene sheets separated with air-filled pores. The 3D graphene aerogel is synthesized using a simple hydrothermal technique followed by freeze-drying and thermal annealing. The resulting graphene aerogel is elastic and exhibits a significant change of electrical resistance with strain. It is found that the resistance of the sample is highly sensitive to applied strain, enabling the detection of small changes of the sample size down to a few micrometers. The responsivity of the samples allows detecting fast events down to a few microseconds. We show that the 3D graphene-based strain-gauge can be used as a wearable electronic sensor for human heartbeat monitoring as well as for other kinds of biological motion detection.

Resume : PAN (Polyacrylonitrile), Rayon and Pitch are three main precursors for carbon fibers where PAN is used mostly due to its good thermal stability, high carbon content and good tensile strength. However, PAN-based carbon nanofibers limit its use in bulk due to the high cost of precursor i.e. PAN. So there is a need to develop carbon fibers from low-cost precursors. Biopolymers such as lignin and cellulose have high carbon content and have the potential to become a low-cost precursor due to their abundance in nature. Lignin is the second most abundant biopolymer after cellulose. Due to the highly complex structure of lignin, it is very difficult to spun it alone in the form of fibers. So, we have blended lignin with PVA (polyvinyl alcohol) and spun the blend using electrospinning. In this work, we present the optimization and synthesis of carbon nanofibers from Lignin: PVA blend using the electrospinning technique. Further, these mats were characterized by their electrochemical properties. SEM analysis shows that lignin: PVA based carbon nanofibers have a diameter in range 600-850 nm. These nanofiber mats were further characterized for their microstructural, thermal and electrical properties using XRD, RAMAN, TGA, DSC, BET. These mats show a specific capacitance of 145F/g at 1A/g.

Resume : In this work, in order to elucidate the intrinsic mechanism of thermal transport along different crystallographic planes in layered materials, we propose a simple and convenient method to manufacture inclined graphite applying Focused Ion beam (FIB). Then, the thermal conductivities along several crystallographic planes in graphite at room temperature are measured using the time-domain thermoreflectance (TDTR) method. To address the issue of lacking in-plane symmetry in inclined graphite, a three dimensional thermal model is developed to extract the thermal conductivity for layered materials from the measured signals of the TDTR method. In addition, for comparison with the cut graphite samples and extracting the in-plane and cross-plane thermal conductivities of graphite sample, a piece of graphite flake is prepared to conduct the TDTR experiment. Our experimental results show that the processing method is reliable and validate the three dimensional thermal model which we develop is appropriate to describe the thermal transport in layered materials. More important is that the results also provide a direct experimental evidence for the classical anisotropy model derived from the Fourier’s law can well predicting the thermal transport along an arbitrary crystallographic plane in layered materials. Furthermore, for graphite, after phonons undergoing the sufficient scattering processes, the in-plane phonon modes dominate the process of thermal transport along all crystallographic planes except the cross-plane direction owing to the value of the in-plane thermal conductivity is much larger than that of the cross-plane conductivity. Our study provides a new perspective on the thermal transport in graphite and other layered materials, and provides an important design guideline for actively manipulating the direction of thermal transport in nano-layered materials.

Resume : Nanographene, a small piece of graphene, has attracted unprecedented interest across diverse scientific disciplines particularly in organic electronics.1 The biological applications of nanographenes such as bioimaging, cancer therapies, and drug delivery would provide significant opportunity and breakthrough in the field. However, intrinsic aggregation behavior and low solubility of nanographenes stemming from the flat structures hamper their development in bioapplications. Herein, we report a water-soluble warped nanographene (WNG)2 that can be easily synthesized by a sequence of regioselective C–H borylation and cross-coupling of saddle-shaped WNG core structure. The high water solubility of water-soluble WNG is ensured by its saddle-shaped structure with hydrophilic tetraethylene glycol chains. The water-soluble WNG possesses a range of additional promising properties such as long lifetime fluorescence, good photostability and low cytotoxicity. Moreover, the water-soluble WNG has been successfully applied for live HeLa cell imaging and photo-induced cell death.

Resume : Self-healing materials inspire the next generation of multifunctional wearables and IoT appliances. Nonetheless, it is crucial to fabricate thin films enabling seamless and conformational coverage irrespective of the complexity of shape and geometry of the surface for electronic skins, smart textiles monitoring body signals, soft robotics, and wearable devices storing energy. Within this context, the layer-by-layer (LbL) technique is a versatile approach for homogeneously dispersing materials into various matrices. Moreover, it provides molecular level thickness control and conformational configuration on virtually any surface. Poly(ethyleneimine) (PEI) and poly(acrylic acid) (PAA) are materials primarily employed in LbL structures due to their intrinsic ability to form restorative composite coatings at room temperature. However, it is still challenging to achieve thin films having high conductivity, good healing strength, and controlled mechanical properties at ambient conditions. Here, PEI and PAA were mixed with conductive materials such as gold nanorods, poly(3,4-ethylene dioxythiophene) polystyrene sulfonate (PEDOT: PSS), reduced graphene oxide and multi-walled carbon nanotubes in distinct LbL film architectures. Electrical (AC and DC), optical (Raman spectroscopy), and mechanical (nano-indentation) measurements were performed to evaluate changes occurring in multilayered structures. Self-healing tests in some composites indicated multiple healings at the same damaged area, without changes in the electrical properties. The results are promising for the manufacture of self-healing conductors by design, as the mechanical properties were balanced with the healing and electrical efficiencies. The formed nanostructures have the potential for creating smart surface layers having unique features that solve technical challenges.

Resume : Osteoporosis is a skeletal disease characterized by bone loss and bone microarchitectural deterioration. The increasing life expectancy calls for innovative and effective approaches to compensate for bone loss. Due to their well-documented regenerative and anti-inflammatory potential, stem cells represent a promising option. The knowledge of bone piezoelectricity and of bioelectricity as a further cue to influence cell fate, in addition to biochemical and mechanical ones, has elicited for the use of physical stimulation together with electroactive materials as smart alternatives for bone tissue engineering. The combination of smart substrates, stem cells and physical stimulation to induce cell differentiation is therefore a new avenue in the field. Biomimetic scaffolds were prepared by combining the conducting polymer PEDOT:PSS with collagen type I, the most abundant protein in bone. Pores sizes, mechanical and impedance properties were measured as a function of scaffolds composition. Two populations of stem cells were used to understand the impact of scaffold composition on cell behaviour. Preliminary electrical stimulation experiments were run to evaluate its use in combination with the developed electroactive scaffolds in the frame of a bioelectronic approach to bone tissue engineering. Recent results on devices developed to assess stem cell differentiation will be presented.

Resume : Since its early days, ex vivo mammalian cell culture has been conducted on flat two-dimensional (2D) glass or polystyrene surfaces. Although 2D cell culture is still widely used, it is known to result in unnatural cell polarity and morphology in addition to lacking the three-dimensional extracellular matrix. These drawbacks are especially evident if the cultivated cells are clinically relevant cell types including but not limited to stem cells. In this context, 2D cultivation is known to interfere with stem cell proliferation and to alter the cell phenotype. In this talk, different approaches to stem cell cultivation, differentiation, and assessment of migration in 3D will be discussed. In particular, biocompatible natural scaffolds for the cultivation of adult human neural crest-derived stem cells and human mesenchymal stem cells of different origins will be presented. Moreover, the impact of 3D cell culture on the regenerative potential of stem cell secretome will be discussed.

Resume : Despite the growing evidence supporting the use of biocompatible materials as vehicles to deliver therapeutics, their clinical application is often limited by challenging biological environments such as accessing the brain due to the blood-brain barrier (BBB). The BBB hinders most molecules from entering the central nervous system from the blood stream, limiting the delivery of drugs and materials into the brain for the treatment of brain malfunctions. Soft matter engineering offers a powerful approach to the design and synthesis of effective systems to manipulate cellular signals and behaviors. Here, we investigate soft biomedical materials as minimally-invasive and transgene-free alternatives for the treatment of brain disorders, including safer strategies to bypass the blood brain barrier, and the development of new technologies for wireless neuromodulation and gene-editing therapies. Nanoscale heating effects of magnetic nanoparticles under alternating magnetic fields has been used to control the thermodynamic transition of thermo-sensitive polymer brushes to release neuromodulatory compounds. This magneto-thermal system allow us to modulate on-demand neural activity, which is critical for the treatment of neurological disorders such as Parkinson disease. In the other hand, pH sensitive biocompatible block co-polymers are being used to fabricate artificial viruses. Gene-editing systems have become an important tool in biological engineering and genome editing, providing programmable platforms for precision gene targeting. These tools have immense promise as therapeutics that could potentially correct disease-causing mutations. Most of the gene-editing approaches use viral vectors to deliver the therapeutic tools, limiting clinical applications due to safety concerns. We investigate stimuli-responsive soft biomedical platforms that enable a synthetic, non-invasive strategy for the delivery of gene-editing tools. Our non-viral delivery approach focuses on mimicking biological organisms? functionalities and engineering them into a synthetic polymeric carrier. Specifically, we have been developing polymeric technologies for the delivery of gene-editing tools across the BBB for the treatment of glioblastoma and other brain cancers.

Resume : Tumor hypoxia not only reduced the efficacy of chemotherapy and radiation therapy but also changed the feature of tumor action. Thus, tumor hypoxia microenvironment needs to be improved urgently. Herein, we report a multifunctional silk fibroin hydrogel (SFG) system that combines artificial and natural enzymes, which integrates platinum-coated-hollow-gold-nanoparticles (HGN@Pt, artificial enzyme) and glucose oxidases (GOx, natural enzyme) in SFG, to develop a starvation and photothermal cancer synergistic therapy. The GOx could consume the intratumoral glucose/oxygen leading to tumor starvation and necrosis, but the strategy was strongly limited in tumor hypoxia microenvironment. Therefore, we designed an efficient, stable biomimetic nanoenzyme (HGN@Pt), which could catalyze the decomposition of H2O2 to generate O2 (e.g., from 0 to 8 mg/L at 37 ? in 10 min). In addition, the HGN@Pt could be utilized as photothermal therapy (PTT) agent due to the strong surface plasmon resonance, thereby converting the near infrared (NIR) light into heat (e.g., from 25 to 50 ? under 1 W/cm2 of 808 nm laser irradiation in 10 min). More importantly, we found that the HGN@Pt display great thermal and catalytic stability, which were advantageous for repeated-photothermal therapy and long-term hypoxia improvement ability, respectively. Moreover, the in vitro experimental results show that the HGN@Pt could catalyze endogenous H2O2 to generate O2, thus the GOx were able to consume glucose to induce starvation therapy, even in hypoxia condition. Note that the H2O2 would be also generated after the oxidation of glucose, which would be converted to O2 by HGN@Pt, again. Therefore, the both catalysts successfully form a complementary circulatory system to continuously consume glucose and generate O2 at tumor site. Finally, we constructed a 4T1 tumor model to investigate the therapeutic efficacy in vivo. The mixture of silk fibroin solution was orthotopically injected at the tumor site, followed by the irradiation of NIR laser for inducing gelation. The multifunctional SFG could slowly release the GOx to tumor microenvironment for long-tern starvation therapy, and trap the HGN@Pt in tumor region to conduct the repeated PTT treatments and continuously improve the hypoxia condition in the treatment period. The results of reduction of tumor tissue hypoxia-inducible factors and tumor inhibition ability clearly demonstrated that the system would efficiently improve tumor hypoxia and successfully inhibit the tumor growth.

Resume : Nanogels are hydrogel-based nanoparticles that are highly tunable in chemical composition and physicochemical properties. These nanoparticles are highly versatile in their uses and allow for several functions to be combined including antimicrobial properties, fluorescence and MRI tracking and imaging, anti-adhesive, controlled release, and responsiveness to various stimuli. Because of this variety of functions and properties, the particles are used in controlled delivery, imaging, theranostic approaches and functional biomedical multi-modal coatings. The studies presented provide insights in the capabilities of such nanogels, the preparation, modification, and the use of them together with biological systems ranging from in vitro studies to in vivo uses. The ease of scaling, the diversity, and ease of applicability make these particles very powerful and tremendously complement the existing nanotoolbox of liposomes, polymersomes, protein-based nanostructures, and inorganic nanoparticles.

Resume : Biomimetic syntheses combine intrinsic functions of bio(macro)molecules with the unique characteristics of synthetic materials to yield composites that mimic the complex structure of natural tissues. The biomimetic synthesis of coordination networks such as metal-organic frameworks (MOFs) is a relatively new concept in the family of bioinspired materials. For instance, the integration of MOFs with enzymes and proteins via biomimetic strategies has shown potential ground-breaking applications in biomedicine, controlled delivery, biostorage, and biocatalysis. Our group has pioneered the use of biomimetically-mineralized MOFs in the control of extracellular matrix component degradation, particularly of fibrillar collagen (the most abundant protein of the human body). Microporous MOFs have been synthesized in situ either as crystalline shells to immobilize collagen degrading enzymes or as protective coatings for native collagen fibrils. Restraining enzyme catalysis and protecting the fibrillar collagen surface are strategies that ultimately envisage the control of collagen catabolism as this physiological process when unbalanced, is implicated in numeral pathological conditions (e.g., metastasis, neurodegenerative disorders, osteoporosis, periodontal disease, etc.). Currently, we are using these concepts in biomimetics and supramolecular chemistry to address a core problem in restorative dentistry: the degradation of dental hard tissues by endogenous endopeptidases.

Resume : Immune cells recognize tumors and viral cells by receptors that bind ligands on the membrane of target cells. The receptor signaling is extensively studied today, yet its mechanism is still obscure. Here, we engineered a nanoscale biochip with patterned activating ligands, and used it as an artificial target cell for study of how the ligand arrangement regulate the cytotoxic activity of Natural Killer (NK) cells ? lymphocytes of the innate immune system. To pattern the ligands, we tethered them to sub-10 nm nanoimprinted metallic dots. By tracking the NK cell response to the matrix geometry, we discovered the minimal ligand distribution needed for NK cell stimulation. We also engineered a multifunctional biochip that spatially control activating and inhibitory receptors, whose balance regulate the self-tolerance of the immune system. The chip contained patterned nanodots of two different metals selectively functionalized with activating and inhibitory ligands. We found that the inhibition of NK cell activity is optimized upon ~40 nm segregation between the two ligands, due to constrains of the flexibility of the cell membrane. Finally, we discovered nanoscale mechanosensing of NK cells by interfacing them with ligand-functionalized nanowires. We assessed forces on 10 pN scale applied by the cells onto the nanowires, and found that while neither the nanowires or ligands alone stimulated NK cells, their combination boosted their immune response, in an analogy to ?AND gate? with independent mechanical and chemical logic inputs. Our findings provide an important insight into the mechanism of NK cell function, and introduce novel tools for the study of the cell function with unprecedented spatial and mechanical resolutions.

Resume : The aim of the work was to create appropriate substrate for organ transplantation utilizing bioactive tissue-based scaffold populated by cells of graft recipient. The described project consists of few stages aiming to create a fully functional tissue. Aortic valves of animal origin were utilized in the study and they were provided background to produce biocompatible tissue for transplantation into humans. Foreign (host) cells are highly immunogenic components of the graft and they are most responsible for graft rejection. Firstly, host cells were removed (decellularization) by various physical methods (acoustic beam, laser light irradiation) without degradation of the extracellular matrix. These methods differ in their effectiveness and they may also cause destructive effect on components of the extracellular matrix (eg. collagen and elastic fibers) resulting in change of biomechanical properties of the graft. Thus decellularization process was controlled by histological and molecular methods. Samples of decellularized valves and aortic wall were fixed for 48 hours in 4% buffered paraformaldehyde and then they were subjected to a routine paraffin embedding. Briefly, each valve was dehydrated in ethanol (in increasing concentrations: 50%, 70%, 80%, 96% alc., absolute alcohol 1, absolute alcohol 1). Then the material was divided into the following parts: (i). ring of the aorta above leaflet, (ii). left side of the leaflet (subjected to decellurization process), (iii). right side of the leaflet (control). Then, the samples were cleared (two changes of xylene), embedded in paraffin (56ºC, two changes of paraffin) finally paraffin blocks was formed. 5 ?m-thick sections were cut on microtome (i). in a plane transverse to the long axis of the aorta (ring of the aorta) and (ii). in plane parallel to the long axis of the aorta (leaflets, left and right fragment). The sections were mounted on poly-L-lysine coated slides, then dewaxed, rehydrated and subjected to histological and histochemical stainings. One of the new tissue decellularization techniques was laser method, carried out using basic radiation of the Nd:YAG laser at wavelength of 1064 nm or its second harmonic at 532 nm. In order to obtain the most pure extracellular matrix with a minimum number of defects. Different beam patterns, different fluencies and numbers of pulses constituting a single exposure were applied. All exposures were carried out with laser pulses of 10-15 ns in duration at a repetition rate of 5 Hz. In the case of a Gaussian beam, irradiations were carried out at an average fluencies of 169 mJ/cm2 and 83 mJ/cm2 for 1064 nm and 109 mJ/cm2 and 56 mJ/cm2 for 532 nm. The number of pulses in a single exposure cycle was 10, 50, 100, 200 or 500. By inserting a scattering window and focusing lens into the beam path, the samples could be irradiated with radiation with a homogeneous distribution of energy in a circular field with a diameter of 5 mm. The irradiations were carried out at 1064 nm, with a fluency of 76 mJ/cm2 or 56 mJ/cm2. A single exposure consisted of 600, 1000, 2000 or 3000 pulses. Direct laser interference lithography was also used for tissue decellularization. The distribution of laser radiation was in the form of circular spots with a diameter of 5.2 µm spaced apart by about 9.1 µm. Irradiations were carried out at 532 nm. The energy of the pulse was 40 mJ, 20 mJ or 10 mJ. 500, 1000 or 2000 pulses were used in a single exposure cycle. Processes were supported by spectroscopic measurements of aortic tissue samples, which allowed to estimate the absorption coefficients, equal to 4.4 cm-1 for 1064 nm and 3.7 cm-1 for 532 nm. The work was performed as part of project OPUS 12, UMO-2016/23/B/ST8/01481 funded by the National Science Centre (NCN) of Poland.

Resume : Nanoparticles (NPs) have emerged as promising tools for the control of unwanted biofilms. However, a fundamental understanding of the role of the biofilm extracellular polymeric matrix (EPS) in NP-biofilm interactions is currently lacking. This work analyses how the EPS matrix affects the interaction between engineered NP and biofilms, thus influencing NP diffusion and bioaccumulation. Two strains of Pseudomonas biofilms were exposed to various families of fluorescent engineered silica NPs, synthesised with different surface composition and charge (functionalisation with epoxy-, amino-, PEG- or alkyl-groups). When NPs were exposed to EPS extract solutions, significant differences in the biomolecular corona thickness and composition were observed for different NP surface functionalisation approaches. The same variation was observed in biofilm experiments: particles with the same charge and size but different surface show a very different uptake (up to 40%) and distribution patterns across the biofilm thickness. Differences were also observed for the same particles interacting with different biofilms. The data show that NP surface chemistry dictates the interaction with the biofilm and selective interactions with the EPS take place according to specific surface functionalisation. The results support the rational design of functional NPs as a platform for the development of NP-based anti-biofilm technology that will overcome the challenges associated with the EPS matrix.

Resume : Heterocyclic compounds play a vital role in the metabolism of all living cells. There are vast numbers of pharmacologically active heterocyclic compounds, many of which are a regular clinical use. Nitrogen and oxygen containing five member heterocyclic compounds have occupied enormous significance in the field of drug discovery process. The pharmacological potential of heterocycles containing the oxazolemoiety was studied, what has enabled the wide introduction of novel farmacological remedies in medicinal practice. As reference molecules we choose substituted 1,3-oxazoles that are an important class of heterocyclic compounds because of their wide spectrum of biological activities. These compounds exhibit a wide range of biological activities, including cytotoxicity, immunosuppression, multiple drug resistance pump inhibition, antibacterial and antiviral activities. They have shown themselves as powerful scaffold in drug design, especially, highly active anticancer agents. In addition, 1,3-oxazole derivatives are useful synthetic intermediates and can be used as diversity scaffolds in combinatorial medical chemistry. This report summarizes the results of the widest investigations of the relationship between the biological affinity and the electron structure of oxazole itself and its main derivatives, as well as comparing these results with the pharmacological testing. Here, the original fragment-to-fragment approach (Pharmacophor molecule-Biomolecule) is proposed for study the interaction between 1,3-oxazole derivatives (as a pharmachophor) and active center of biomolecule. The main characteristics of the electron structure (optimized molecular geometry, charge distribution, energies and shapes of molecular orbitals) were calculated by DFT/6-31 (d,p)/wB97XD method (package GAUSSIAN 09)

Resume : Elastic composite-based piezoelectric energy harvesting technology is highly desired to enable a wide range of device applications, including self-powered wearable electronics, robotic skins, and biomedical devices. Recently developed piezoelectric composites are based on inorganic piezoelectric fillers and polymeric soft matrix to take the advantages of both components. However, there are still limitations such as the weak stress transfer to piezoelectric elements and the poor dispersion of fillers in matrix. In this talk, a highly-enhanced piezocomposite energy harvesters (PCEH) is representatively developed using a three-dimensional (3D) interconnected electroceramic skeleton by mimicking and reproducing the sea porifera architecture (although the speaker will introduce other research examples and achievements). This new mechanically reinforced PCEH is demonstrated to resolve the problems of previous reported conventional piezocomposites, and in turn induces stronger piezoelectric energy harvesting responses. The generated voltage, current density and instantaneous power density of the biomimetic PCEH device reach up to ~16 times higher power output than that of conventional randomly-dispersed particle-based PCEH. This work broadens the further developments of high-output elastic piezocomposite energy harvesting and sensor application with biomimetic architecture.

Resume : We developed a type of zero-valent iron nanoparticle (ZVI NP) that exhibits selective anti-cancer potency through non-apoptotic cell death in several cancer types. In human head-and-neck cancers (HNC), we demonstrated that ZVI NPs selectively induce cancer ferroptosis yet spare the normal cells and presented strong efficacy in human cancer bearing rodent model without detectable systemic toxicity. Mitochondria and lysosome dependent pathways play critical roles in the ZVI NPs induced cancer cells death. Further investigation revealed that 10 ferroptosis associated gene panel may serve to predict their susceptibility to ZVI NPs treatment. Combination of ferroptosis inducers with ZVI could reverse ZVI therapeutic resistance. In addition, we also discovered that ZVI NPs inhibited the allograft growth of mouse Lewis lung carcinoma. Strikingly, multi-color fluorescent-immunohistochemistry demonstrated that the infiltrated M1 macrophages increased in tumor site whereas M2 macrophage located toward the tumor periphery after ZVI NPs treatment. ZVI also significantly down regulate PD-L1 in tumor infiltrating T cells. These results suggested that ZVI NPs inhibit tumor growth in vivo through both direct induction of cancer cell ferroptosis and modulation of tumor microenvironmental immune system towards anti-cancer phenotype.

Resume : Nowadays, problems of energy crises and climate change pose a threat to human living. Therefore, developing eco-friendly cooling systems is an utmost issue to work on. Most of current cooling methods require energy to carry heat away. By means of passive radiative cooling, the system can radiate heat to outer space through the atmospheric transmission window between 8-13 ?m, thus lowering the temperature without any energy consumption. Some photonic solar reflector and thermal emitter, like HfO2, SiO2 and metamaterial film, can reflect incident sunlight while emitting radiation in the atmosphere windows. However, with its complicated fabrication and high cost, nanophotonic approach is hard to scale up to meet the requirements of commercial applications. Meanwhile, we focus on natural materials of great potential which are still not well-studied. Compared to the typically narrow Infrared (IR) emissivity peaks of artificial daytime cooling materials, the extremely broadband emissivity peak of the natural materials could cover two atmospheric windows (8-13 ?m and 16-25 ?m). Here, we present a study on silk cocoon, which is characterized by its 90% absorption at IR wavelengths and simple, well-studied fabrication process for different morphologies. We fabricate silk fibroin thin film with thickness ranging from 6 to 88 ?m by adjusting the concentration of silk fibroin solution. We observe the broadening of thickness leads to an increase in emissivity over IR wavelength regions, indicating thickness is the key factor to optical and radiative control. In addition to simulated spectra, optical constants of silk film are considered for further analysis. We also investigate the board band absorption and extinction coefficient at NIR wavelength. Throughout the IR wavelength, silk film exhibits a maximum absorbance of 92% at the thickness of 100 ?m. However, absorbance of silk film has positive correlation with thickness in solar spectrum region, resulting in high Psun performance. Therefore, thermal simulation is applied to find the lowest Tequ, at which the optimal thickness of silk film is located. Finally, we conduct temperature measurement on silk film practically to verify its daytime radiation cooling ability. With silk covering, the temperature of mobile phone decrease by 3.5 K, while the average absorbance of mobile phone is significantly enhanced to 94 % in atmospheric window.

Resume : Mesoporous silica nanoparticles (MSNs) is a promising nanocarrier for delivering anti-tumor drugs to cancer. Polyethylene glycol (PEG) has been linked to many nanocarriers to increase the dispersity, bioavailability, and circulation time of nanoparticles. However, on the other hand, PEGylation could limit the cellular uptake and endosomal escape of MSN, resulted in significant loss of activity of the delivery system. In this study, to overcome the ?PEG dilemma?, we synthesized pHR-MSN-PEG/DA@EPIs, in which pH-responsive (pHR) core-shell MSNs were utilized as nanocarriers, the anti-tumor drug epirubicin (EPI) was encapsulated by electrostatic interaction, and the amine-containing (DA) functional groups were introduced to control the loading and release of EPI. In vitro studies showed that the plain pHR-MSN-PEG/DA is non-toxic and the cleavage of PEG from carriers was achieved in response to an acidic environment, result in high efficiency of cellular uptake. In addition, pHR-MSN-PEG/DA@EPIs showed considerable cytotoxicity towards 4T1 tumor cells. For in vivo studies, pHR-MSN-PEG/DA showed excellent passive targeting behavior due to the enhanced permeability and retention (EPR) effect, and strong tumor inhibition effects in a chicken embryo chorioallantoic membrane (CAM) tumor model.

Resume : Overcoming the immunosuppressive tumor microenvironment is critical to realizing the potential of cancer immunotherapy strategies. Recent evidences are emerging to show that the cyclic di-guanylate (c-di-GMP), a molecular adjuvant, could induce the production of type I interferons (IFNs) via the stimulator of interferon genes (STING) dependent pathway in antigen presenting cells (APC), leading to enhance the tumor immunogenicity. However, the efficacy of negatively charged c-di-GMP may be limited by some inherent shortcomings, including the poorly membrane permeable, rapid clearance and the inefficiency of cytosolic delivery. Hence, we attempt to develop an alternative ?in situ vaccination? approach based on nanotechnology to initiate an antitumor immune response. In this study, PEGylated RITC fluorescent mesoporous silica nanoparticles (MSN) with a positively charged molecule (N-trimethoxysilylpropyl-N,N,N-trimethylammonium chloride, TA) by co-condensation was synthesized to form RMSN-PEG/TA. The characteristics of nanoparticles were determined by transmission electron microscopy (TEM), dynamic light scattering (DLS) and nitrogen adsorption-desorption isotherm. The anionic c-di-GMP was loaded into cationic RMSN-PEG/TA via electrostatic interactions (c-di-GMP@RMSN-PEG/TA), showing the loading amount of c-di-GMP on c-di-GMP@ RMSN-PEG/TA was around 3 wt%. RAW264.7 cells treated with c-di-GMP@ RMSN-PEG/TA obvious increased the production of IL-6, IL-1?, and IFN-? analyzed by real-time PCR, as well as the expression level of phospho-STING (Ser365) protein investigated by western blot. The mouse 4T1 breast tumor-bearing Balb/c mice received injection of c-di-GMP@ RMSN-PEG/TA revealed dramatically tumor growth inhibition accompanied by the infiltration of activated CD11c+ dendritic cells and CD4+ T cells at the tumor site detected by flow cytometry. We validate this in situ vaccination by STING pathway activation provides an attractive therapeutics for breast cancer, highlighting its potential to improve clinical outcomes of cancer immunotherapy.

Resume : Introduction The most common cancer in women is breast cancer and it continues to affect millions of people worldwide. Survival rate increases with early detection but diagnostic procedures may also put patients at risk because of radiation exposure. Development of alternatives such as near-infrared diagnostics may be the key to this problem. Fluorescent dyes may be used but due to their intrinsic characteristics, modification or encapsulation must be done to make it biocompatible. With this, biopolymers may be employed as carriers or encapsulating agents. Experiment Synthesis of polyester-based amphiphilic block copolymers was carried out by ring-opening polymerization reaction. The critical micelle concentration of the copolymers were measured followed by the encapsulation of 2QMEH, a two-photon fluorescent dye. The optimal copolymer for 2QMEH encapsulation showing a loading efficiency of 68.6% was selected. Results and Discussion Encapsulation of 2QMEH gave a two-photon absorption (TPA) cross section of around ~55-120 GM at 820 nm. This is significantly greater than the threshold value for biological applications showing a good potential for in vivo bio-imaging to be used together with near-infrared for breast cancer diagnosis. Acknowledgements: The authors would like to thank the Ministry of Science and Technology of Taiwan for the financial support under grant number MOST 108-2119-M-033-002. References 1) M.L. Gou, X.L. Xheng, K. Men, J. Zhang, L. Zheng, X.H. Wang, F. Luo, Y.L. Zhao, X. Zhao, Y.Q. Wei, Z.Y. Qian, J. Phys. Chem. B., 113, 39 (2009). 2) M. Drobizhev, S. Tillo, N.S. Makarov, T.E. Hughes, A. Rebane, J. Phys. Chem. B., 113, 4 (2009).

Resume : Our ability to control cell behavior by properly engineered materials and microenvironments is tightly coupled to understanding the mechanisms of cell-matrix interactions. Anisotropy of extracellular matrix (ECM) drives cell alignment and directional migration during processes like development and wound healing, but also in cancer cell migration and invasion. So far, migrational persistence whether on flat isotropic or anisotropic surface patterns and fibers was mostly studied as local phenomenon asking how specific integrins are responsible for the recognition of the spatial ECM cues. Yet, cell alignment and directional migration in response to external ECM cues requires signal integration across length scales. By producing patterned 2 µm ECM stripes, which lead to cell alignment, and testing the previously described pan-integrin null fibroblast cells, we indeed observed that cell alignment and directional migration on patterned stripes were lost when ?1 integrin was absent. By combining nanopillar arrays with printed cell-adhesive fibronectin (FN) stripes, we could probe subcellular force distributions at submicron resolution. While it was previously recognized that the ?v- and ?1-class integrin signaling pathways are coupled, via myosin II contractility, we discover here that myosin III coupling of these integrin signaling pathways requires a stiff cell nucleus. Importantly, directional migration along adhesive patterned stripes was also impaired for lamin A/C knockout cells, incapable of forming an actin cap and restored upon lamin A/C rescue. Together, our data suggest that ?1 integrin is required for the recognition of spatial ECM cues and that force transmission to the nucleus via lamin A/C is essential for subsequent directional migration.

Resume : The unique functionalities of polyelectrolyte brushes depend on several types of specific interactions, including solvent structure effects, hydrophobic forces, electrostatic interactions, and specific ion interactions. Subtle variations in the solution environment can lead to conformational and surface structural changes of the polyelectrolyte brushes, which is discussed mainly from a surface interaction perspective in this review. We highlight the use of these surface-grafted polymer films to create functional surfaces for various applications, including non-fouling surfaces, boundary lubricants, as well as stimuli-responsive surfaces. Based on the SFA and AFM methods, the impact factors for constraining the lubricity of polyelectrolyte brushes have been investigated. Experimental results reveal that the charged polymer chains and the osmotic pressure of the counterions can lead to wear resistance and low friction in monovalent salt solution. However, the lubrication can break down in the presence of multivalent counterions, even at very low concentrations, resulting from electrostatic bridging and brush collapse between chains from apposing surfaces and changes in surface topology. This study helps to give some insight into the interchain interactions contained in polyelectrolyte brushes but also can promote their application in many technical, medical, physiological, and biological areas. Additionally, we investigated the structure and antifouling properties of surface tethered zwitterionic peptide monolayers with different peptide chain lengths and charge distributions using a combination of surface plasma resonance (SPR), atomic force microscopy (AFM), and all atomistic molecular dynamics (MD) simulation techniques. Our results demonstrate that longer zwitterionic peptides exhibit better antifouling performance. The patchy charge distributions of the positive and negative charges in the peptides, although affecting the structure of the peptide molecules, do not significantly change the antifouling properties of the peptide monolayers.

Resume : In this lecture, we will discuss the use of surface-modified nanoparticles such as quantum dots and mesoporous nanoparticles (MSNs) for bio-imaging. The applications of surface-modified nanoparticles for pH sensing will be first introduced. We will present two ratiometric pH sensor designs using water-soluble, dual-emission, Mn2+-doped quantum dots (Qdots) decorated with D-penicillamine (DPA-MnQdots) and mesoporous silica nanoparticles (MSNs) modified with two different pH-sensitive dyes, fluorescein isothiocyanate (FITC) and Oregon green (OG), and a reference dye, rhodamine B isothiocyanate (RITC). The behavior of these surface-modified nanoparticles in cells will be discussed. For in vivo imaging, we will present the study of real-time circulating tumor cells (CTCs) and cancer stem cells (CSCs) 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.

Resume : Bioelectricty is reported to be one of the key regulators of morphogenesis in vivo and electrical potentials have been reported to influence a number of physiological processes. Bioelectronics materials and devices are able to interact with living systems (e.g., tissues, organs, cells). They are indeed able to translate an ionic signal into an electronic readout and they are also able to deliver stimuli influencing ion movements therefore affecting specific target functions (e.g., tissue regeneration).

Resume : In this study, we employed a novel one-step electrospinning process to fabricate poly(ethylene oxide) (PEO)/poly(3,4-ethylenedioxythiophene): polystyrenesulfonate (PEDOT:PSS) core/shell nanofiber structures with improved water resistance and good electrochemical properties. We then integrated a biocompatible polymer coating with three-dimensional (3D) PEDOT-based nanofiber devices for dynamic control over the capture/release performance of rare circulating tumor cells (CTCs), as well as the label-free detection by using organic electrochemical transistors (OECTs). The detailed capture/release behavior of the circulating tumor cells was studied using an organic bioelectronic platform comprising PEO/PEDOT:PSS nanofiber mats with 3 wt % (3-glycidyloxypropyl)trimethoxysilane as an additive. We have demonstrated that these nanofiber mats deposited on five-patterned indium tin oxide finger electrodes are excellent candidates for use as functional bioelectronic interfaces for the isolation, detection, sequential collection, and enrichment of rare CTCs through electrical activation of 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.

Resume : Medical applications of multifunctional nanoparticles are expected to be one of the most important possibilities in innovative medicine. Organosilica nanoparticles are novel nanomaterials that are prepared from a single organosilicate coupling agent (organotrialkoxysilane) such as 3-mercaptopropyltrimethoxysilane. Organosilica nanoparticles are both structurally and functionally different from typical silica nanoparticles (inorganosilica nanoparticles) prepared from tetraalkoxysilane. The organosilica nanoparticles contain both interior and exterior functionalities such as mercaptopropyl residue as prepared. The organosilica nanoparticles allow for facile surface and internal functionalization, offering new opportunities to create multifunctionalized nanoparticles. Over the last two decades, research on the internal functionalization of organosilica nanoparticles has evolved. Various sizes of fluorescent organosilica nanoparticle containing various types of fluorescent dye including near infrared (NIR) dye can be prepared using a one-pot synthesis. In addition, functional fusions of organosilica nanoparticles and other functional nanoparticles such as quantum dots, gold nanoparticles, and iron oxides are possible based on organosilica particles technology. These multifunctionalized organosilica nanoparticles are useful for various imaging techniques such as in vivo imaging, cell labeling, time-lapse fluorescent imaging, and multimodal imaging. Multifunctionalized organosilica nanoparticles have high potential to create novel imaging systems and provide novel information of cell characteristics and functions. In recent year, we have launched additional research on surface functionalization of organosilica nanoparticles using biomolecules and polymers. Surface-functionalized organosilica nanoparticles revealed various alterations of the interaction with cells including tumor cells and macrophages. We applied multifunctionalized NIR organosilica nanoparticles to tumor-bearing mouse. The particles showed an accumulation on tumor tissue on NIR in vivo imaging, and damaged tumor cells by using photodynamic effect. Imaging and therapy using multifunctionalized organosilica nanoparticles allow for nano-theranostics.

Resume : My laboratory has been developing various types of activatable and dual-targeted photosensitizing agents as smart theranostics for selective near-infrared fluorescence imaging and photodynamic therapy (PDT) of cancers and inflammatory diseases. Recently a fucoidan-based theranostic nanogel (CFN-gel) consisting of a fucoidan backbone, redox-responsive cleavable linker, and photosensitizer was developed to achieve activatable near-infrared fluorescence imaging of tumor sites and an enhanced PDT to induce the complete death of cancer cells. A CFN-gel has nanomolar affinity for P-selectin and VEGF. Moreover, a CFN-gel is non-fluorescent and non-phototoxic upon its systemic administration due to the aggregation induced self-quenching in its fluorescence and singlet oxygen generation. After internalization into cancer cells and tumor neovascular endothelial cells, its photoactivity is recovered in response to the intracellular redox potential, thereby enabling selective near-infrared fluorescence imaging and an enhanced PDT of tumors. It also provides a significant antitumor effect in the absence of light treatment in vivo. Our study indicates that a fucoidan-based theranostic nanogel is a new theranostic material for imaging and treating cancer with high efficacy and specificity.

Resume : Cell adhesion is a requisite stage in a number of physiological and pathological processes, such as cell differentiation, immune responses, and tumor metastasis. The process of cell adhesion is composed of three steps, cell-substrate contact, cell spreading, and cytoskeleton reorganization. Conventional adhesion assays, such as colorimetric and fluorometric detection, are time-consuming and insensitive. Tracking of cell morphological changes is often difficult to quantify. In the past decades, surface plasmon resonance (SPR) is widely applied in biosensing technology due to the rapid, real-time and label-free characteristics. Here, we developed a novel metal nanoslit-based biosensor with a detection platform of transmissive surface plasmon resonance (t-SPR). The platform can determine cell adhesion by Fano resonance signals, which are changed during cell binding to the nanoslit. Therefore, we can simultaneously analyze the focal adhesion and cell spreading through the spectral peak and dip of the Fano resonance. The peaks and dips reflect the long- and short-range cellular changes, respectively. We previously examined the features of cell adhesion and found that this method has great potential for estimating the thickness of adherent cells and the metastatic potencies of lung cancer cells. Metastasis, a complicated process in which cancer cells spread from a primary tumor to distant sites via the circulatory system, is the main cause of death in cancer patients. In light of this fact, we are now screening commercial drugs like ion-channel inhibitors and G protein-coupled receptors (GPCR) compounds which are related to cell adhesion and might involve in metastasis. The screening could reveal candidates which may be used as anti-metastasis drugs.

Resume : Molecular environments inside cells are surprisingly crowded with numerous number of biomolecules. About 40 percent of the cell volume is occupied by biomolecules. Biochemical reactions are subject to be temporally, spatially, and specifically controlled. From biochemical and biophysical point of views, it is incredible that selective interactions and specific functionalization of biomolecules in the temporal and spatial-specific manner can be achieved under the complex molecular crowding environments. One of the key futures to achieve the specific interaction of biomolecules is collective biomolecular behavior. In recent years, biomolecular localization and compartmentation systems using droplets via liquid-liquid phase separation (LLPS) inside cells, become one of the most hot research topics in biology. Droplets are temporarily formed, and their formation is reversible and responsive to various external signals, which are in contrast with aggregation of biomolecules which is generally irreversible. In this presentation, we will show a model system of a droplet in a test tube, in which we use nucleic acids (RNA and DNA) which forms G-quadruplexes and arginine-rich peptides which do not have any stable structure. By mixing these two components, a rapid LLPS was observed. It was suggested that the G-quadruplex structure is critical for undergoing LLPS. In the talk, we would like to discuss property of the droplet as a biomaterial.