Advanced biomaterials: elaboration, nanostructure, interfaces with tissues

Resume : The necessity for biomaterials with bone-like mechanical properties in order to increase implant-bone compatibility led to the conception of a titanium-polymer composite material1. To create a strong interface, the two materials are attached through covalent bonds. To achieve this, the titanium surface undergoes a structuring alkaline (NaOH) treatment prior to the adsorption of a phosphonic acid-containing polymerization initiator. A polymer brush (PMMA here) is then grown from the modified titanium surface via controlled radical polymerization2 (ATRP). Here we present the multi-technique characterization of the titanium-polymer construct. SEM imaging of cross-section cuts obtained through cross-polishing is correlated with electrochemical measurements (impedance spectroscopy, cyclic voltammetry, corrosion rate analysis), polarization-modulated infrared reflection absorption spectroscopy (PM-IRRAS), ellipsometry, X-ray photoelectron spectroscopy, water contact-angle measurements, scratch-tests and chromatographic size estimations on the degrafted polymer. In particular, we show that the preparation conditions of the titanate and of its subsequent chemical modification strongly influence the thickness, morphology and porosity of the polymer brush and can thus be tuned to achieve specific properties. References: (1) Reggente, M.; Masson, P,; Dollinger, C.; Palkowski, H.; Zafeiratos, S.; Jacomine, L.; Passeri, D.; Rossi, M.; Vrana, N.E.; Pourroy, G.; Carrado, A. ACS Appl. Mater. Interfaces 2018, just accepted. (2) Vergnat, V.; Pourroy, G.; Masson, P. Polym. Int. 2013, 62 (6), 878–883

Resume : Vapor-based functional poly(p-xylylenes) constitute a versatile class of reactive polymers that can be prepared in a solventless process via chemical vapor deposition (CVD) polymerization. The resulting ultra-thin coatings are typically pinhole-free, and the resulting thin polymer provide consistent coatings, which decouple the underlying substrate surface properties and can be applied for surface modification on most of the substrate geometry and materials. More importantly, equipped functional groups can serve as anchoring sites for tailoring of biointerface properties via immobilization of biomolecules. Recent developments have enabled more advanced interfacial properties for the coatings including multifunctional coatings for multitasking, route-controlled conjugations to immobilize biomolecules and to provide orthogonal biological activities, surface composition gradients, and to integrate with patterning techniques to render chemical and topological confined surface properties. These advanced polymer coatings have shown to manipulate the cell growth activities in cell attachments, cell proliferations, stem cell spheroids formation, and the controlled over cell differentiation pathway, as well as enhancing stem cell capacity to trans-differentiate into multiple cell lineages in the mesoderm, endoderm and ectoderm.

Resume : Plasma polymerization (PlzP) method is a common way to control the thickness of film growth down to angstrom (Ao) size with a uniform coating over the substrate materials. This method enables us to preserve the bulk properties of the main material to be used. Especially, adjustable chemical composition of the thin film achieved by plasma modification has become vital over the years, that directly influence the performance and the functionality of the polymers for desired application. At this point due to their positively charged property, amine-rich thin films step forward for biotechnological applications. They can provide covalent bonding with negatively charged biomolecules such as enzymes, DNA or living cells. However, high amine concentration affects the thin films? stability negatively because of the magnitude of the surface energy. To overcome this problem two different hydro-carbon groups which are n-Hexane(HEX), and n-Heptane(HEP) were applied to the surface by plasma polymerization before amine-rich coating. The main reason of selecting hydro-carbon group is; pre-coating can be a key tool since this coating has high degree of cross-linking as well as having thermal and chemical stability compared to other polymer thin films. Thus, this work has three different surfaces that are; pre-coating with HEX, following Ethylenediamine(EDA) which is selected as a precursor for amine-rich coating, pre-coating with HEP, following EDA, and single layer coating with EDA. In order to examine these modified surfaces; glass slides and Quartz Tuning Forks(QTF) were selected as substrates. QTF could potentially facilitate the detection of bonded biomolecules on to the surface because it is a very well-known mass sensitive transducer. These three different films examined from first day to the thirtieth day by using Contact Angle, Frequency and Resistivity measurements. PlzP conditions were selected to be 1, 5, 10 min for exposure periods and 25, 50, 75 and 100 W power. After completing the surface functionalization step, Glutheraldehyde (GA) [2,5% (v:v)] applied to the thin film surfaces for activating amine groups with aldehyde. To check GA performance a model protein, Bovine serum albumine (BSA), was used to control the binding performance of modified and activated surfaces. For investigate the interaction between fuctionalized surface and biomolecules, Antiochratoxin-A (A-OTA) and Ochratoxin-A (OTA) was used. BSA experiments were provided optimum concentration values, so OTA concentration decided. Attenuated Total Reflectance-Fourier Transform Infrared (ATR-FTIR) and Contact Angle measurements chosen for the aging tests which shows properties and characteristics of thin film layer on specific days. After these steps in order to get further information about thin film layer morphology, Scanning Electron Microscopy (SEM), and Atomic Force Microscopy (AFM) techniques were used. The surfaces of the thin films? were analyzed by X-Ray Photoelectron Spectroscopy (XPS). Contact Angle measurements showed that, two steps PlzP samples are more stable than single step PlzP samples, this mean; the surfaces which contain hydro carbon groups, effects directly the performance and long-term stability of amine-rich surfaces. Two different hydro carbon surfaces showed that molecular weight and binding energies effect the thin film directly. This study leads a potential development of a biosensor platform for detection of antibody, toxins etc. in all types of environment.

Resume : Titanium is widely used in orthopedic implants for its excellent resistance to corrosion and its biocompatibility.1 Nevertheless and despite the prevention rules, 1,5% of implanted prostheses are still subject to bacterial infections. That’s the reason why chemical modification of titanium surfaces to confer desirable functional properties is required. Bioactive polymers bearing ionic groups have good antibacterial properties and can improve osseointegration.2-6 In this context, we have developped three different techniques of poly(sodium styrene sulfonate) (polyNaSS) covalent grafting onto titanium (Ti) surfaces and study the influence of their architecture on biological response.2-6 Two of them are “grafting from” techniques requiring an activation step either by thermal or UV irradiation.2-4 The third method is a “grafting to” technique involving an anchorage molecule onto which polyNaSS synthesized by RAFT polymerization is clicked.5 The advantage of the “grafting to” technique when compared to the “grafting from” technique is the ability to control the architecture and length of the grafted polymers on the Ti surface and their influence on the biological responses.5,6 This study compares the effect of three different grafting processes on the in vitro biological responses of bacteria and osteoblasts. Overall outcomes of this investigation confirmed the significance of the sulfonate functional groups on the biological responses, regardless of the grafting method.5,6 1. Klabunde Windler M., Titanium in medicine. Berlin: Springer, 2001, 703-746. 2. Migonney V. et al., Patent WO/2007/141460, 2006. 3. Falentin-Daudré C. al., Patent WO/2017/025519, 2016. 4. Chouirfa H. et al., RCS Advances, 2016, 6, 13766-13771. 5. Chouirfa H. et al., Biointerphases, 2017, 12, 02C418. 6. Chouirfa H. et al., ACS Applied Materials & Interfaces, 2017, DOI: 10.1021/acsami.7b14283.

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Resume : After the introduction of biomaterials into the body, adhesive proteins adsorb to the surface of implants and play a critical role in bacterial interactions. To modulate these interactions and try to prevent subsequent bacterial infection, one strategy consists in developing bioactive coatings at the surface of materials. In this work, the grafting of biphosphonated dendrons (BP-D) on oxide surfaces was performed and showed some suitable properties for antimicrobial coating applications. The chemical structure of these dendrons was designed to allow in one step a strong anchoring on the surfaces through phosphonated moieties, with the prospect of improving the antifouling character of the bare material. Another great interest was the presence of specific -COOH end groups that were able to be functionalized with antimicrobial biomolecules such as poly(arginine) (PAR).1-2 Prior to PAR grafting, BP-D were deposited on silicon dioxide surfaces and characterized by QCM-D, contact angle and AFM. Taken together, all analyses indicated the presence of a homogeneous monolayer of BP-D at the surface. Serum protein adsorption revealed a strong decrease of the amount of adsorbed molecules when compared to the bare material. Then, the efficiency of PAR grafting was evidenced by fluorescent microscopy. Hence, promising coatings for antibacterial applications were developed here. Ref. 1. Özçelik et al. P. Adv. Healthc. Mater. 2015 4 2026-2036 2. Mutschler et al. Chem. Matter. 2017 29 3195–3201

Resume : Hydrogels can be used as scaffolds for tissue engineering and actuators for optofluidic devices. Smart hydrogels that can withstand consecutive and high-level load-unload cycles are ideal candidates for load-bearing applications. However, combining stimuli responsiveness with toughness and self-healing properties has been challenging. To address these requirements, we integrated robust polyurethane (PU) hydrogels with hydrogels reinforced by dipole-dipole and H-bonding interactions (PAAA) to form double network (DN) gels and bilayered actuators. The DN gels show rubber-like behaviour while exhibiting self-healing and shape-memory properties, which together make these structures promising candidates for building artificial cartilage or muscle. As an alternative approach, we developed thermally-responsive PAAA-PU bilayered actuators for building soft manipulators. In this configuration, the PAAA gel with thermo-sensitive volume change property acts as responsive swelling layer while PU gel serves as a non-swelling support layer. The actuators are programmed to specific shapes by mismatch of swelling ratios between two layers. The proposed materials expand the scope of hydrogel applications in robotics and medicine.

Resume : Superparamagnetic iron-oxide nanoparticles (SPIONs) are the keystone of an expanding number of biomedical applications ranging from diagnostics and drug delivery to magnetofection and theranostics, just to name a few. In particular, their unique properties as contrast agents for Magnetic Resonance Imaging (MRI) has made them very attractive for the elaboration of a new generation of biomedical scaffolds for tissue engineering. In this context, several research groups have looked into associating SPIONs to biodegradable polymers like polylactic acid (PLA). However, the synthetic approaches proposed so far have not allowed a proper control over the PLA/SPION interface, leading to a loss of the intrinsic shape and/or biodegradation properties of the biopolymer. Here, we will present a novel approach to covalently attach a monolayer of SPIONs at the surface of PLA scaffolds (including PLA microfibers prepared by electrospinning), which widely overcomes the drawbacks of previous synthetic procedures. The suitability of these new hybrid materials for biomedical applications will be demonstrated, through MRI analyses as well as cytotoxicity analyses.

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Resume : The main aim of this study was to analyze the kinetics of the calcium phosphates layers formation process after immersion in SBF on laser-modified titanium surface. For this purpose, Ti grade 2 sheets were functionalized using the DLIL (Direct Laser Interference Lithography) technique in order to obtain the surface with periodic and hierarchical patterns. The method presented within this study was developed in order to locally functionalize the surface of prefabricated elements with the original roughness. The fabrication of the multimodal topography can be used to take the advantage of favourable micro- and nano-roughness and to mimic the bone hierarchical surface structure after the remodelling process. Furthermore, appropriately designed texture of the surface may be beneficial for the osteogenic passes of the stem cells. The hierarchical topography with roughness in the range of nano- to micrometers was characterized in terms of the shape, roughness and chemical composition. In order to obtain a set of information, the numerous research methods have been used: scanning electron microscopy, optical profilometry, atomic force microscopy and X-ray photoelectron spectroscopy. The process of apatite formation on the patterned titanium surface in a simulated body fluid was thoroughly investigated by correlating the SEM observations as well as X-ray photoelectron spectroscopy (XPS) and Fourier-transform infrared spectroscopy (FTIR) measurements. Determination of the topography features and the surface properties, which have a decisive impact on the growth of the calcium-phosphate layers, can be used as an effective tool for manufacturing the controlled surface structures and thus improving of the bone?implants interactions. This research was financially supported by The National Science Centre Poland under Grant no. 2016/23/N/ST8/02044.

Resume : In-situ crosslinking scaffolds have attracted scientist’s attention recently as they can be administered into the defects with sophisticated shapes in minimally invasive manner. Chitosan hydrogels with desirable physiochemical properties have been studied as injectable scaffolds for tissue engineering applications recently. Although they have prominent characteristics like antimicrobial properties, biocompatibility, biodegradability, availability and low cost; however, their weak mechanical properties limit their practical usage especially for engineering of certain tissues with high stiffness (like cartilage). To address this need, thermo-responsive chitosan based hydrogels with improved mechanical properties were prepared in this research. Rheological properties of the hydrogels such as storage shear modulus, gelation time and gelation temperature were investigated. It was observed that these properties can be tuned using different hydrogel formulations. Results showed that the hydrogel storage shear modulus can be improved from 2±0.3 up to 200±0.8 kPa by chitosan modification. Besides, gelation time and temperature can be varied depending on hydrogel formulation. Furthermore, hydrogel morphology evaluations confirmed the hydrogel porous structure suitable for tissue engineering applications. Thus, our novel thermo-responsive chitosan based hydrogels with improved mechanical properties can be considered as proper injectable scaffolds for engineering of certain tissues.

Resume : The liquid - liquid interface can be used as a suitable medium for generating some nanostructured films of metals, or inorganic materials such as semi conducting metals. Such interfaces have novel applications in fabrication of biosensors, and electrochemistry at the liquid - liquid interfaces was shown to be a viable technique for drug sensing. These processes can be controlled well if we study the dynamics of nanoparticles at the liquid-liquid interface which is a new field of study, and is not understood well yet. We investigated the dynamics of nanoparticles at liquid-liquid interfaces using numerical modeling by solving the fluid-particle and particle-particle interactions. Our work is based on the Phase Field Method (PFM) in addition to the Molecular Dynamics (MD), in which we superimpose the discrete model of particles motion on the continuum model of fluids which is a new idea in numerical modeling and it may be of great importance in many systems within computational physics. We modeled liquid-liquid interface using the diffuse interface model, where the interface is considered to have a characteristic thickness. We have shown that the concentration gradient of one fluid in the other gives rise to a hydrodynamic force that drives the nanoparticles to agglomerate at the interface. These obtained results may introduce new applications where certain interfaces can be considered to be suitable mediums for the synthesis of nanostructured materials, and this will help us to improve the application and usage od biosensors in different domains. In addition some liquid interfaces can play the role of effective filters for different species of biological nano-particles and solid state waste nanoparticles, which will be very important in many industrial and biomedical domains.

Resume : Studying of how different signaling pathways spatially integrate in cells requires selective manipulation and control of different transmembrane ligand-receptor pairs at the same time. This work explores a novel method for precisely arranging two arbitrarily chosen ligands on a micron-scale 2D pattern. The approach is based on lithographic patterning of Au and TiO2 films, followed by their selective functionalization with Ni-NTA/histidine and biotin/avidin chemistries, respectively. The selectivity of chemical and biological functionalizations is demonstrated by XPS and immunofluorescence imaging, respectively. This approach is applied to produce the first of their type bi-functional surfaces with controllably positioned ligands for activating receptors of natural killer (NK) immune cells. NK cells were used as a model system to demonstrate the potency of the surface in guiding site-selective cell attachment and activation. Upon applying the suitable ligand or ligand-combination, surfaces guided the appropriate single- or bi-functional attachment and activation. These encouraging results demonstrate the effectiveness of the system as an experimental platform aimed at the comprehensive understanding of the immunological synapse. The great simplicity, modularity and specificity of this approach makes it applicable for a myriad of combinations of other biomolecules and applications, turning it into the “Swiss knife” of bio-interfaces.

Resume : Understanding biomineralization processes carries an important medical significance. As one of its applications, the in vivo deposited calcium phosphate layer on bone implants can help to avoid the typical adverse host response and achieve a direct bonding with the bone. In fact, the prediction of in vivo implant behaviors by the use of easy-to-perform in vitro experimental methods is of great interest in the biomaterials research. Previously, Kokubo proposed an in vitro method using simulated body fluid (SBF) by observing calcium phosphate crystal formation on implant surface after certain duration of immersion into this SBF. However, the nucleation is a subtle process that is sensitive to many external factors, often leading to inconsistent results using this method. In this project, we proposed a new in vitro protocol based on a titration procedure. Calcium solution is constantly added to the phosphate solution containing the implant material until nucleation takes place, as monitored by a calcium electrode. The degree of supersaturation needed for the nucleation provides a good indication of the biocompatibility of the material. Four titanium-based surfaces with different chemical treatments were tested. Cell culture and animal experiments using sheep were also conducted as a validation of the correlation between in vitro and in vivo results. Torque tests and measurement of bone-implant-contact area were used as a quantitative indication of the biocompatibility.

Resume : Motor Proteins provide nanoscale transport at the intracellular level. As a complementary tool to nanofluidics, these bio-motors have also been envisioned for nanotechnological devices. Because of the motors’ functional complexity, their mechanisms can best be understood in-vitro, where functional parameters can independently be controlled. I will report on work that studies and harnesses the transport properties of motor proteins on functionalized structures, such as carbon nanotubes,[1] micro-electrodes,[2] micro-wires [3] and loop tracks.[4] We have also developed devices that are useful in in-vitro investigations of neuro-degenerative diseases, like Alzheimer’s disease.[5] In addition to these applications, motor proteins allow the study of the cluster formation dynamics in active elements.[6] In such devices, we observe and model the hierarchical emergence of chiral symmetry breaking, a result that can shed light on one of the most important unsolved questions in the development of life: What causes the chiral asymmetry of living organisms? [1] A. Sikora, et al. Nano Lett. 14, 876 (2014). [2] J. A. Noel, et al. ACS Nano 3, 1938 (2009). [3] K. Kim, et al. Biomed. Microdev. 16, 501 (2014). K. Kim, et al. Appl. Phys. Lett. 105, 143701 (2014). [4] A. Sikora, et al. ACS Nano 9, 11003 (2015). [5] S. Bhattacharyya, et al. Int. Biol. 8, 1296 (2016). S. Bhattacharyya, et al. Adv. Biosys. 1, 1600034 (2017). ibid 1, 1700108 (2017). [6] K. Kim, et al. Phys. Biol. 13, 056002 (2016).

Resume : Bone defects often occur as a result of trauma, bone tumors, resection, and metabolic diseases. These defects are typically reconstructed using either a natural bone graft or an artificial synthetic bone graft. This paper studied the production and properties of bioceramics bone graft substitutes from duck-derived bone particles, as a natural source. Poly(𝜖-caprolactone) (PCL), 𝛽-tricalcium phosphate (TCP), and poly(lactic-co-glycolic acid) (PLGA) are widely used as synthetic materials for tissue engineering. This study aimed to investigate the osteogenic capacity of duck-derived bioceramic (DB)/PCL/PLGA hybrid scaffold on large segmental defects in a rabbit model. The in vivo performance of 48 healthy New Zealand White rabbits, weighing between 2.5 and 3.5 kg, was evaluated. The rabbits were assigned to the following groups: Group 1 (negative control), Group 2 (PCL/PLGA hybrid scaffolds), Group 3 (PCL/TCP/PLGA hybrid scaffolds), and Group 4 (PCL/PLGA/DB hybrid scaffolds). A 5-mm large defect was induced in the diaphysis of the left rabbit radius. Radiology, micro-CT, and histopathological findings were evaluated at 0, 4, 8, and 12 weeks after scaffold implantation. Furthermore, bone formation markers (bone-specific alkaline phosphatase, carboxyterminal propeptide of type I procollagen, and osteocalcin) were evaluated. As an alternative material to the autogenous bone, duck-derived beak bone particles for bone substitute had attracting great attention due to its biological properties. This study demonstrated that duck-derived beak particles can be prepared as economical bone graft substitutes of natural, biological origin hydroxyapatite.

Resume : Three-dimensional (3D) printing is one of attractive way for the direct fabrication of bio-ceramic bone institute as like a scaffold with a computer aided design which can be applied for orthopedic surgery by extruding through a micro-nozzle to form a patient customized shape. The advantage of 3D printing method is to easily create for specific shapes that normally cannot produce with traditional scaffold fabrication methods such as sponge socking, fiber bonding, freeze drying, etc., as well as, many studies have adopted this way for bone substitute scaffolds, to make optimized structures with required pore shape, size, and interconnectivity of 3D printing outcomes. Recently, CaO-SiO2-P2O5-B2O3 glass ceramics has been reported to improve the osteoblastic differentiation of human mesenchymal stem cells, can read for better bonding to adjacent bones compared with hydroxyapatite. Therefore, the purpose of this study was to investigate the material characteristics of 3D printed bioactive glass scaffolds with varying of porous structure. The principal material was CaO-SiO2-P2O5-B2O3 glass ceramic powder which has mixture with selected binder to produce ceramic slurry, the scaffolds were fabricated with fused deposition modeling (FDM) 3D printing technique with change of cubic lattice structure by controlling of extruding pressure to be 30~70 % porosity and angle offset with 0°, 45°, and 90° for varied stacking structures, then sintered at 1100 °C for 24 h. The surface morphology and 3 dimensional stereology were analyzed by field emission-scanning electron microscopy (FE-SEM) and micro-computed tomography (µCT) to make sure pore shape and size, material composition and crystal structure were obtained by energy dispersive X-ray spectroscopy (EDS) and X-ray diffraction (XRD), respectively. The mechanical properties with different stacking structures were experimented by 3 point bending, static compression, and nano-indentation test. As a preliminary result, a porosity has highly correlated with higher fracture strength and frequent crack paths, the highest fracture resistance was occurred with 45° of extruding angle offset applied. Acknowledgement: This work was supported by Advanced Technology Center (ATC) Project (10077279) funded by the Ministry of Trade, Industry and Energy (MOTIE) of Korea. Keywords: Bio-glass, 3D printing, Porosity, Mechanical property, Patient customizing

Resume : Poly-ether-ether-ketone (PEEK) interbody fusion devices (cage) are widely used to treat spinal disorder such as degenerative disc disease and spine instability. A kind of PEEK cage has a main advantage that is similar elastic modulus with native bone can minimize the effect of subsidence rates, while has a disadvantage to do not integrate between PEEK cage and surrounding bone tissues. In order to overcome a drawback of the PEEK cage, titanium coated PEEK cage is being introduced to compensate disadvantage of non-coated PEEK surface to minimize failure of surgery. Despite numerous number of clinical report, a study for biomechanical behavior by surface modification are unusually limited, needed more detailed research results. Therefore, the purpose of this study was to investigate the comparison of biomechanical properties between bare PEEK cage and titanium coated PEEK cage with compressive strength, subsidence, and expulsion test by using of material testing machine (MTS System Co., MN, US). Each 18 number of un-coated PEEK cage and titanium coated PEEK cage (GS Medical Co., Ltd., Korea) specimens were fabricated with medical grade PEEK material, and confirmed to be a same size (25mm(L) x 11mm(W) x 15mm(H) & lordotic angle 8∘). In case of titanium coating, the surface of PEEK cage was modified by the method of vacuum plasma spray to be a coarse surface. The mechanical properties were analyzed with static compression, subsidence, and expulsion test, these were accorded by ASTM standard F2077, F2267, and the study of Vijay K Goel et al, respectively. The results of this study indicated that titanium coated PEEK cage (699N) showed 69% higher ultimate load than un-coated PEEK cage (413N) by the expulsion test, while the compressive yield load and subsidence results were not showed a strong contrast by titanium coating on PEEK cage. According by these results, a titanium coated PEEK cage could be expected to provide the initial stability in postoperative results with having low incidence of expulsion compared to un-coated PEEK cage.

Resume : Predicting the droplet state accurately is significant in manufacturing rough surfaces with superhydrophobic properties. We use molecular dynamics simulation to investigate the static behavior of the water droplet on solid surfaces featuring pillared structures. Results show that the droplet in either the Wenzel state or the Cassie state depends on the height of the pillars and the pillar surface fraction. There is a critical point of the transition between the Cassie state and the Wenzel state when the height of the pillars and the pillar surface fraction changes. All simulations are performed based on the LAMMPS package. To investigate the droplet behavior on the solid surface, a graphite surface of 25 nm long and 25 nm wide and an initial water box of dimensions 5*5*5 nm3 (3921 water molecules) are built. The CHARMM (Chemistry at Harvard Macromolecular Mechanics) force field is employed. The present study employs the TIP3P water model that has a single Lennard-Jones center representing an oxygen atom together with three charges, 0.834e for the O atom and +0.417e for the H atoms with an angle of 104.52° between the atoms. The solid surface representing graphite with the characteristic surface energy of 0.0355 kcal/mol and a van der Waals radius of 3.4 Å is treated as a rigid body and there is no relative motion between solid atoms. The long-range electrostatic interactions are calculated using the PPPM (particle–particle particle-mesh) method and the Lennard-Jones potential is truncated at a cutoff radius of 14 Å. The NVT ensemble which keeps the number of atoms, volume and temperature constant is used with a Nosé-Hoover thermostat at 298 K. The thermostat applied on the water molecules avoids the temperature rise caused by artificial vibration. A periodic boundary condition is applied for the three dimensions of 250*250*250 Å in the x, y, and z directions, respectively, and the solid surface locates on the x–y plane. Newton’s equation of motion is integrated numerically using the velocity Verlet algorithm for 1–2.5 ns with a time step of 2 fs. To investigate the droplet static behavior and dynamic transition caused by vibration, the smooth surface and 15 types of rough surfaces are established. The water molecules are arranged on the rough solid surface as a rectangular block initially as shown in Fig. 1. Quadrangular pillars are arranged with lateral size 10*10 Å and three different gaps in the x and y directions 6*6 Å, 10*10 Å and 15*15 Å, respectively, and the height of the pillars is changed from 3.35 to 16.75 Å for every gap size. All simulations are performed in two stages. The purpose in the first stage is to evaluate the nanostructure influence on the droplet state, the Wenzel or the Cassie. To achieve it, the computation is carried out for 1.5 ns. Then, in the second stage the sinusoidal vibration with various amplitudes and frequencies is applied to the smooth and rough surface in the z direction. Especially on the rough surface, to investigate the dynamic state transition of the water droplet in the presence of vibration, a large number of simulations are performed and the thresholds are observed that could induce the transition from the Wenzel state to the Cassie state. The static state of the water droplet in the Wenzel or Cassie state depends on the height of the pillars and the pillar surface fraction in the absence of vibration. For the low pillar surface fraction of case P3, the droplet is more inclined to be in the Wenzel state except that the height of pillars is greater than 20.1 Å. Conversely, if the pillar surface fraction is very large such as the case P1, the droplet will exhibit the Cassie state from a moderate height of 6.7 Å. It can be found, there is a critical point of the transition from the Wenzel state to the Cassie state when the pillar surface fraction is 0.16 and the height of the pillars is 20.1 Å. To the contrary, there also is a critical point of the transition from the Cassie state to the Wenzel state when the pillar surface fraction is 0.39 and the height of the pillars is 6.70 Å.

Resume : Chitosan (CS) and cellulose nanofibril (CNF) are well-known biopolymers which are prepared from the most abundant organic materials in nature of chitin and cellulose. Hydroxyapatite (HAp)-CS composite known as a bone scaffold is mechanically weak in aqueous environments due to the swelling of CS so that it could not be used for applications such as an internal fixation device of bone fracture. Polylactic acid (PLA) derived from renewable resources such as sugar cane is biocompatible and biodegradable but brittle and become acidic when degraded. Here four-component (CNF-HAp-CS-PLA) composite was studied where PLA as a continuous phase compensates CS weakness while basic CS reduces acidity of PLA and CNF is reinforced for enhancing mechanical properties such as brittleness of PLA. The composite was fabricated by following steps; gelation of mixture of HAp nanoparticle and CS in acidic solution followed by drying and pulverization, surface modification of CNF, and mixing HAp-CS and surface-modified CNF with PLA using a melt mixer. Mechanical properties such as flexural and tensile strength of the composite were tested. And the composite was used for locking compression plate of internal fixation of bone fracture of a rabbit.

Resume : Various types of transmembrane pores and ion channels in the range of 1-100 nm are found in each biological cell, playing crucial roles in varieties of significant physiological activities such as maintaining cell osmotic balance and stabilizing cell volume. Inspired by this natural phenomenon, different biomimetic nanodevices (nanopore/channel) with different characteristics have emerged as an attractive and powerful platform and have been used for a wide range of applications. Generally, the principle of analysis applications based on solid nanopore/channel can be described as follows: molecules access or attach on the inner surface of a nanopore/channel, change the effective diameter of the nanopore/channel, or affect the charge transfer as well as the wettability of the inner surface (or the confined space) of the nanopore/channel, leading to ionic current changes that can be detected. Among this solid nanopore/channel-based detection and analysis, the strategy in which the capture/recognition element of the target analyte was functionalized or modified onto the inner surface of the nanopore/channel has usually been adopted. In these strategies, the captures/recognition elements specifically interact with their target analytes, forming a “complex” of different dimensionalities depending on the recognition mechanism and generating signal changes of different amplitude.

Resume : Porous microbeads synthesized by water–oil–water double emulsion solvent evaporation method show great potential as bio-carriers for bacteria attachment. Poly (lactic-co-glycolic acid (PLGA) was chosen as a biodegradable and biocompatible candidate to fabricate the porous microbeads. The effect of concentration of ammonium bicarbonate and poly vinyl alcohol (PVA) as well as the surface modification technic were discussed here. Finally, the fluorescence bacteria were well attached to these porous microbeads. The confocal laser scanning microscopy (CLSM) was used to survey the inner porous structure without cutting of microbeads to obtain a cross-section image. The open structure porous microbeads whose surface was modified by NaOH solution were compared with non-open porous ones based on bacteria attachment. The TNT (trinitrotoluene) and DNT (dinitrotoluene) sensitive bacteria were attached on open porous microbeads and the sensing behaviors of TNT and DNT as a function of time were surveyed. Porous PLGA microbeads loading with fluorescence bacteria can be a candidate as a bio-sensor to detect the existence of TNT or DNT. Key word: PLGA, Porous microbeads, bacteria attachment, TNT and DNT detection

Resume : Recently, three-dimensional printing includes a wide variety of manufacturing techniques, which are all based on digitally-controlled depositing of materials (layer-by-layer) to create freeform geometries. We have developed an aqueous-solvent-based micro-molding technique for creating polymeric, bio-degradable micro-structures which can be loaded with delicate bioactive therapeutic agents. The arrays of microneedles are integrated in an out-of-plane fashion with a base plate and can serve as patches for the release of drugs and vaccines. We used soft lithography and micro-molding to manufacture ceramic nanoporous. The process enables the incorporation of emerging protein based vaccines into sophisticated micro structures, e.g., microneedles, without damaging their biological efficacy as conventional (UV- or temperature-based) micro-molding processes would. As a demonstration, we successfully fabricated microneedles loaded with a peptide complex using a polydimethylsiloxane (PDMS) mold, including the parameters to be controlled. The process is proven to be capable of molding microneedles with sufficient sharpness (down to 45 ?m radius of curvature at the tips) to penetrate skin and exhibit transfection of peptide complexes, which can be used for designing customized drug delivery systems using 3D structures with biomaterials. This work was supported by a grant to the Next-Generation BioGreen 21 Program (no. PJ01337101), Rural Development Administration, Republic of Korea.

Resume : The discovery of graphene and its unique properties [1], has stimulated increasing interest in the study of materials with layered structures. Lead iodide, as a direct band gap semiconductor of about 2.5 eV, is characterized by a spatial repetition of three planes, I-Pb-I and can be applied in medicine, X-ray and gamma spectroscopy. Doping of PbI2 single crystals by transition metal (TM) elements (Mn, Fe, Co etc) with unfilled 3d-shell is of interest for the development of new materials- layered diluted magnetic semiconductors. In recent times, a number of research works have been reported on the synthesis of low-dimensional structures of PbI2:TM by physical and chemical methods. All low-dimensional structures, as similarly to for the bulk crystals, demonstrate anisotropy of properties and a strong exciton confinement. In this work, we report on studies of interactions between PbFeI2 nanoparticles (NPs) and model proteins type of human serum albumin (HSA). To probe this interaction, in addition to conventional UV-Vis absorption and photoluminescence spectroscopic methods we have used micro-Raman spectroscopy. It was shown the changes of protein luminescence spectra after adding of semiconductor nanoparticles in appropriate colloidal solution. The UV-vis absorption spectra of the proteins have also changed because of formation of NPs–HSA biocomplex. These findings provide crucial information on a interaction of NPs with human blood components and significantly allows to extend the potential applications as the components of modern diagnostic systems. 1.Geim A.K., Novoselov K. S., The rise of graphene, Nat. Materials 6, 183-191 (2007).

Resume : Introduction: Placing eye prostheses after eye enucleation is often associated with eye infections. It is known that silver cations have antibacterial activity. They act as antioxidants, blocking cellular processes and leading to bacterial cell death. The principle of its action is to block the flow of oxygen to pathogenic microorganisms. Pathogenic microorganisms die quickly after contact with positive silver ions. These microorganisms do not develop colloidal silver resistance. In this aspect, silver particles have a stronger antibiotic effect. Purpose: Application of silver antibacterial nanoparticles on ocular dentures. Material and Methods: An ophthalmic prosthesis is made of two materials, transparent and dense. The transparent material is made of Superacryl, and the Superpont® C B is dense. A specialized vacuum system for high frequency magnetron sputtering with argon carrier gas was used to apply silver nanopowder. The starting chamber pressure is 10-2 Pa. The silver target used is of high purity silver (sample 999). The pattern is heated during deposition of the silver nanosilver to 50 degrees. Results: The obtained silver nanopowder is 12 nanometers thick on the experimental eye prosthesis specimen. An even nanosilver was observed on the test specimen, both on its transparent and on its non-transparent inner part. The antibacterial action of silver nanoparticles against gram positive, gram negative bacteria, as well as Candida albicans has been established. Conclusion: Antibacterial nanoparticle is applied for the first time on ocular dentures. Applying a silver anti-bacterial layer will reduce eye infections when inserting and using eye prostheses. References: 1. Składanowski M, Golinska P, Rudnicka K. Evaluation of cytotoxicity, immune compatibility and antibacterial activity of biogenic silver nanoparticles. Med Microbiol Immunol. 2016;205(6):603–613. 2. Li WR, Xie XB, Shi QS, Zeng HY. Antibacterial activity and mechanism of silver nanoparticles on Escherichia coli. Appl Microbiol Biotechnol. 2010;85(4):1115–1122. 3. Durán N, Durán M, de Jesus MB, A new view on mechanistic aspects on antimicrobial activity. Nanomedicine. 2016;12(3):789–799..

Resume : The development of low-molecular-mass oleogelators (LMOGs) that are able to entrap and structure oils has spurred growing interest in food, cosmetic and pharmaceutical industries in recent years. Oleogels that contain edible oils, such as soybean oil, sunflower oil, corn oil, olive oil, etc. have proven to be “green” ingredients for health, food and personal care products. Gels of petroleum-derived hydrocarbons are also appealing to the oil field industries for various applications, such as oil recovery and toxicity remediation devices. Recently, we have discovered some amino acid- derived LMOGs that can gelate a number of vegetable and mineral oils at low concentrations. A number of non-steroidal anti-inflammatory drugs (NSAIDs), e.g. diclofenac sodium, ibuprofen, ketoprofen, etc. was solubilized in the oleogels. Furthermore, the LMOGs can efficiently uptake common fuel oils, such as petrol and kerosene from their biphasic mixture with water, thus showing great implement in the remediation of spilled oil from industrial wastewater. The properties of the oleogels, including morphology, thermal and mechanical stabilities will also be discussed in this oral presentation.

Resume : Periodontitis is defined as a chronic inflammation resulting in irreversible destruction of the periodontium, which consists of the hard (i.e. alveolar bone and cementum) and soft (i.e. gingiva and periodontal ligament) tissues surrounding and supporting the teeth. The design of scaffolds which mimic the complex periodontal shape and organization represents a significant challenge in regenerative periodontology. We prepared a biomimetic matrix using nondenatured collagen type I (COL), chondroitin 4-sulfate (CS, Sigma) and fibronectin (FN, Sigma) in a weight ratio of 10:1:0.005. The mixture was conditioned as 3D porous scaffold by lyophilization. In order to evidentiate the microstructure of the biomimetic scaffold we used scanning electron microscopy (SEM) and immunohistochemistry for detection of CS and FN. Preliminary tests of their cytotoxicity in fibroblast gingival culture were performed by MTT assay. SEM showed 3D porous ultrastructure with interconnected pores formed between COL fibrils. The scaffold contains uneven pores with size ranging between 50-250 μm, suggesting its ability to promote cell infiltration, proliferation and adhesion. Immunofluorescence showed a random distribution of CS among COL fibers, some COL fibers being associated with more CS than others. FN appears to be firmly attached to COL surface, suggesting the existence of interaction between these components. Cytotoxicity tests indicated high values of cell viability (> 80%). This work was supported by a grant of Ministery of Research and Innovation, CNCS-UEFISCDI, project number PN-III-P4-ID-PCE-2016-0715, within PNCDI III.

Resume : Bioactive molecules, though present in small quantities in foods and plants, are substances that provide great health benefits. However, they are also sensitive to a number of factors such as light, temperature, and oxygen. Hence, in order to maximize their efficiency, it is important to stabilize these molecules and to find ways in preventing them from degradation. Inorganic lattices with 2D structure are often adopted to increase their thermal and photo stabilities and antioxidative activity. In the present work, layered double hydroxides (LDHs) and layered rare earth hydroxides (LRHs) are compared as host materials for such a purpose. LRHs are structurally similar to LDHs consisting of positively charge rare-earth hydroxide layers with exchangeable, charge balancing anions in the interlayer space. LDHs have already shown promising applicabilities in various fields such as health care, drug delivery, food, etc. while LRHs are recently being studied for their potential uses as adsorbents, catalysts, and additives. The exchange capacity and arrange mode of anions in the interlayer galleries of LDHs and LRHs depends on the net positive charge of their hydroxide layers. The positive charge density of LDHs with general formula M²⁺_1-xM³⁺_x(OH)₂A^n-_x/n·mH₂O (A = interlayer anions) is controllable by adjusting M²⁺/M³⁺ ratio, whereas LRHs with general formula RE₂(OH)₅A^n-_1/n·mH₂O (RE = rare earths) have a fixed charge density. Hence, it was expected that they exhibit significantly different inclusion and release behavior and capability as host materials for pharmaceutical and cosmeceutical molecules. As representative examples, the inclusion phenomena of common bioactive molecules such as cinnamate, salicylate, caffeate and retinoate were compared in the interlayer space of LDHs and LRHs. The similarities and differences were established depending on the nature of host – guest interactions.

Resume : [Introduction] Ion channels are membrane proteins that play crucial roles in transmembrane signaling. Reconstitution of ion channels in artificial bilayer lipid membranes (BLMs) provides a well-defined system for investigating the functions of ion channels and screening drug effects acting on them. However, the instability of BLMs hindered the widespread application of the BLM systems. To improve the stability of BLMs, we previously reported on combination of BLM formation and microfabrication.1 Micro-apertures having nano-tapered edges were fabricated in silicon dioxide (SiO2)/silicon nitride (SiN) septa and BLMs formed in the aperture showed improved mechanical stability. In this study, we tried to further improve the stability of the BLMs by surface modification of the SiO2/SiN septa. BLMs were formed in SiO2/SiN septa which were treated with various modifiers and the relationships between the properties of the modified surfaces and the stability of BLMs were investigated. [Exeperimental] SiO2/SiN/Si substrates were immersed in several silane coupling agents, octadecyltrichlorosilane (OTS), 3,3,3-trifluoropropyldimethyl-chlorosilane (FPDS), (tridecafluoro-1,1,2,2-tetrahydrooctyl)trichlorosilane (PFTS), (tridecafluoro-1,1,2,2-tetrahydrooctyl)dimethylchlorosilane (PFDS), (heptadecafluoro-1,1,2,2-tetra- hydrodecyl)dimethylchlorosilane (PFDDS) and 3-cyanopropyldi methylchlorosilane (CPDS), for modifying the surface of the substrates. Water contact angles and hexadecane contact angles were measured. Diffusion coefficient of lipid monolayers formed on the modified SiO2/SiN/Si substrates were evaluated based on fluorescence recocery after photobleaching (FRAP). SiO2/SiN/Si chips with microapertures were silanized by the above-described procedure. BLMs were formed in the modified SiO2/SiN/Si chips by the folding method and evaluated the stability of the BLMs in terms of tolerance to an applied fcentrifugal force with and without proteoliposomes and tolerance to movement of water surrounding BLMs by buffer aspiration. [Results and Disucssion] SiO2/SiN/Si substrates modified with long perfluorocarbons (PFDS, PFDDS) showed high lipophobicity, while those modified with a short perfluorocarbon (FPDS) or a short hydrocarbon (CPDS), showed low lipophobicity. Lipid monolayers formed on the substrates that were treated with PFDS and PFDDS showed higher diffusion coefficient than those formed on the CPDS-modified substrates. Then we prepared BLMs in SiO2/SiN/Si chips treated with PFDS and CPDS, and compared their mechanical stabilities. It was found that the stability of the BLMs formed in PFDS-modified chips was superior to those formed in CPDS-modified ones in terms of tolerance to an applied cenrifugal force in the presence of proteoliposomes and tolerance to water movement induced by repetitive vertical displacement of the water surface. These results suggest that the stability of free-standing BLMs is dependent on the surface property of the substrate that suspends the BLMs and that BLMs on highly lipophobic surfaces are mechanically stable. Thus, this simple appoarch for the formation of stable BLMs should contribute to development of high-throughput drug screening devices for ion channel proteins. [References] [1] A. Hirano-Iwata, et al. Langmuir 26 (2010) 1949–1952. [2] A. Hirano-Iwata, et al. Biophys. J. 110 (2016) 2207–2215. This work was supported by CREST program of the Japan Science and Technology Agency. :

Resume : Recently, nanomaterial-based drug delivery systems are extensively investigated for controlled release of the carried drugs in order to maintain concentrations at the desired levels for an extended period of time. To date, many kinds of inorganic compounds have been employed for constructing these systems, including layered double hydroxides (LDHs). It was expected that the layered rare earth hydroxide family (LRHs) could also be applied for nanohybrids slowly releasing active ingredients because of its high anion exchangeability between the hydroxocation layers where a large variety of inorganic/organic anions can be sheltered. More importantly, it is possible to endow LRHs with a photoluminescence capability by doping activator ions such as Ce³⁺ , Eu³⁺ , and Tb³⁺ into matrices. In the present work, a nonsteroidal anti-inflammatory agent, salicylic acid (2-hydroxybenzoic acid), was intercalated into the interlayer gallery of layered gadolinium hydroxide (LGdH) via direct ion-exchange reaction. As generally observed in organic-inorganic hybrid systems, the thermal stability and photostability of salicylate were significantly improved after intercalation due to electrostatic interactions with the host layers, confinement in the two-dimensional interlayer space, and protection from the attack of atmospheric oxygen. In vitro release studies revealed that this nanohybrid in saline solution could effectively facilitate the salicylate diffusion by significantly increasing the release time. In particular, when Tb³⁺ was doped in host (LGdH:Tb), salicylate intercalation led to the characteristic ⁵D₄ → ⁷F_J (J = 6, 5, and 4) green emissions of Tb³⁺ by its sensitization followed by energy transfer (LGdH:Tb-Sal). The “luminescence-on/off” behavior of LGdH:Tb provided a useful technique for “in-situ” monitoring the inclusion and release of salicylate.

Resume : Many problems associated with Ti implants occur at the metal prosthetis-body interface. In order to eliminate them and improve the mechanical and chemical stability of this interface, the Ti surface is usually coated with a biocompatible thin film. We deposited TiNx films starting from a metallic target on highly polished Ti samples by a magnetron rf-sputtering technique under a mixture of Ar-N2 atmosphere to investigate the role of structure and composition on their properties. The structural properties of the deposited films were investigated using the grazing incidence X-ray diffraction and X-ray reflectivity measurements (XRR) performed in several locations. The chemical composition was investigated by X-ray photoelectron spectroscopy, while the adhesion and hardness, elastic modulus and wear properties of the films were investigated by nanoindentation, scratch and wear tests. The surface morphology was investigated using atomic force and scanning electron microscopy. Wettability investigations were also performed to assess changes in hydrophobicity of coated Ti surfaces. Electrochemical measurements involving corrosion and electrochemical impedance spectroscopy studies were carried out in physiological solutions at room temperature to evaluate the chemical stability of the titanium, bare or covered with the grown films and to compare their performance. The results showed that the deposition of protective coatings improved the stability of the Ti surface, which was less affected by corrosion. Also, the coated surfaces exhibited better mechanical properties than bare Ti.

Resume : Infectious diseases caused by bacterial pathogens are a serious public health risk worldwide. Antibacterial materials including antibiotics, are typically used to control infections. However, their extensive use has resulted in the emergence of antibiotic resistant pathogens, resulting in therapeutic failures. This has prompted us to explore new strategies to control and mitigate risk associated with such pathogens. One strategy to control infection is the use of UV-light active materials, to improve the antibacterial activity. However, the toxic effect of UV has limited its applications. Herein, we have developed a unique antibacterial system by exploiting the peroxidase-like catalytic activity (NanoZyme) of copper oxide nanorods (CuO NRs). The antibacterial activity mainly originates from the decomposition of H2O2 that is catalysed by CuO NRs to generate hydroxyl radical (.OH). Further, the favorable band gap characteristics of CuO allowed us to use visible light as an external ‘trigger’ to modulate the affinity of CuO NRs to H2O2. Our investigations reveal that in comparison to non-illuminated conditions, the rate of hydroxyl radical production increases by ~20 times under visible light illumination, resulting in enhanced antibacterial performance. The strategy of using light activatable NanoZymes as antimicrobial agents will allow widespread applications paving a way forward to control the biocatalytic activity using light as a modular switch.

Resume : Injectable hyaluronic acid has been employed as one of promising materials for tissue engineering due to its unique physicochemical and biological properties. Here, we proposed a method for preparing injectable aldehyde hyaluronic acid/gelatin amine (CHO-HA/Gel-NH2) hydrogel attributed to the Schiff-base reaction encapsulating gelatin nanoparticles (GNPs) or positive charged lysine modified GNPs (GNPs-lysine). The crosslinking reaction did not include any initiators and resulted in fast gelation less than 5 min without cytotoxicity regardless of the presence of gelatin particles. The incorporation of gelatin nanoparticles and the crosslinking density affected the property of the final hydrogel composites such as the equilibrium swelling ratio, morphology, rheology properties and the percentage of degradation. The swelling ratio and in vitro degradation of hydrogel displayed that hydrogels with GNPs and GNPs-lysine had a slower weight loss rate than the control hydrogel without particles. Furthermore, storage modulus (G’) of hydrogel containing 30 mg/ml of GNPs and GNPs-L-lysine were 2,500 Pa and 3,500 Pa, which were higher than the CHO-HA/Gel-NH2 (1,750 Pa) while the microstructure exhibited homogeneous distribution and interconnected porous structures (100~200 micrometers). Thus, the results demonstrated a potential of CHO-HA/Gel-NH2 hydrogel containing GNPs and GNPs-lysine as injectable hydrogel in tissue engineering.

Resume : The three-dimensional (3D) printing technology is very interesting technique due to its potential use to fabricate the appropriate artificial substitutes. Use of this system can design improving scaffolds with customized shape and fully interconnected porous structure. Due to these advantages, 3D printed-scaffolds can be gained to mimic native tissue and to create the appropriate environment for cell attachment, proliferation, and differentiation. Bioprinting techniques, which can construct three dimensional structures with biocompatible materials and cells, have gained great attractions for various biomedical applications. For a successful bioprinting, scaffolds are critical to ensuring the processibility of printing and the biocompatibility of biomaterials. In this study, we fabricated a polycaprolactone (PCL) blended with polyethylene glycol (PEG) 3D printed scaffold using a rapid prototyping system. The PCL/PEG scaffolds exhibited small pores on the filament surface which served to increase hydrophilicity as well as improve cellular proliferation and total protein content. We suggest that the presence of small pores on the scaffolds can be used as an effective tool for tissue engineering and regenerative medicine. These scaffolds can be considered useful as the artificial substitute for bone tissue engineering applications.

Resume : Peptide amphiphile scaffolds can self-assemble into various nanoarchitectures, such as micelles, cylinders, tubes, and vesicles, in aqueous solution. Among them, one-dimensional nanofibers can form the physical hydrogel via entanglement of fibers using non-covalent interactions. Indeed, supramolecular peptide hydrogels have been largely explored in tissue engineering biomaterials on account of their remarkable bioactive, biocompatible and stimuli-responsive features. However, these hydrogels have low mechanical properties and are inclined breakage under mild disturbance. This fragility considerably limits the practical biomedical applications due to easily erode to water. Here, we engrafted the visible light-induced cross-linking which is not harmful to living organisms to supramolecular peptide-based hydrogel for the enhancement of mechanical strength. The mechanical strength was controlled by the amino acid sequence, especially the position of cross-likable tyrosine moiety. These controlled hydrogels offer us to contol the gasotransmitter drug release.

Resume : The biomaterials functionality into the human body, are driven not just by its physical and mechanical properties and also by degradation and bioactivity which are important processes, subsequently involved in the osseointegration of metallic implants. The main goal of this work was to enhance the antibacterial properties of hydroxyapatite (HAP) by Ag addition and to observe the Ag effect through in vitro studies. The coatings were prepared using a RF-magnetron sputtering method. As acellular solutions the following media have been used: simulated body fluid (SBF), Dulbecco's Modified Eagle's medium (DMEM) and phosphate buffer solution (PBS) over a period of 21 days of immersion. Also the corrosion investigations in all three solutions were carried out. Results about the resistance to Candida albicans, Staphylococcus aureus or Salmonella Typhimurium or Streptococcus pyogenes were presented. The results indicate that the dissolution of Ag doped coating provides a stronger driving force for nucleation and growth of new phases in vitro than the undoped hydroxyapatite. Probably this effect is due to Ag which favours the dissolution process through which a sufficient amount of Ca2+ ions that are necessary for CaP nucleation are released, leading to a localized increase of pH which favour the formation of new HAP phase. We acknowledge the support of the Romanian National Authority for Scientific Research and Innovation, project no. 117PED/2017, as well as Core Program 2018.

Resume : An increasing demand for implants significantly accelerates the development efforts on designing the new biomaterials and improving their properties by the technological treatments. A substantial difference in stiffness between the human bones (Young modulus of about 30 GPa) and current biomaterials, like Ti and Ti-6Al-4V alloy (110-120 GPa) or Co-Cr alloys (240 GPa) prevents the stress transfer to adjacent bone. This phenomenon is called the stress shield effect and is manifested in bone resorption around the implant and consequently loosening of the implant leading to a necessary revision surgery. A new group of beta Ti alloys responds to the above-mentioned requirements, offering a remarkably low Young modulus value in the range of 40-70 GPa. The Ti-29Nb-13Ta-4.6Zr alloy, composed of a single beta phase, stable even after the plastic deformation is offering a very low Young modulus value (about 60 GPa). The strengthening ability of Ti-29Nb-13Ta-4.6Zr alloy and potential changes in its functional properties after the SPD treatment are currently unknown. The SPD methods are used in biomedical applications, because they retain excellent bulk properties, such as favorable mechanical properties, high fatigue strength, and improved wear and corrosion resistance properties when required. Therefore, the main aim of this study was the analysis of the influence of grain refinement on the structure and the physicochemical properties of the surface oxide layer. In this contribution, a detailed characterization of surfaces by correlating the contact angle and surface free energy, SEM, XPS and optical profilometry measurements was presented. The protein adsorption tests were conducted with Bovine Serum Albumin (BSA) – the simplest and the most abundantly occurring protein in the human body (at low concentration) in order to evaluate the initial state of ossointegration. The energy of the protein adsorption process was evaluated by the pendant drop and sessile drop measurements of protein solution. This work was supported by the National Science Center in Poland Grant No. 2016/21/B/ST8/01965.

Resume : Current study describes silver nanoparticles which were synthesized using as reducing agents the pigments from Pelargonium domestic and Vitis vinifera in pursuance to manufacture hybrid materials and to evaluate their antimicrobial photodynamic effect and cytotoxicity. The hybrid material was characterized by spectroscopy and electron microscopy techniques. As a first result, UV-vis spectra showed an absorption in the range of 320nm to 700nm. Besides, synthesized silver nanoparticles exhibited spherical shape and a pigment-dependent average size. Silver reduction from Ag+ to Ag0 was evaluated using cyclic voltammetry and X-ray diffraction. Moreover, photodegradation was assessed by Fourier Transform Infra-Red spectroscopy comparing the natural pigment and the hybrid material. In this study, three different concentration of silver nitrate were tested per natural pigment in order to synthesize silver nanoparticles. We herein shown that green synthesis using Pelargonium domestic pigment enhanced the stability of the substituent group from the natural pigment when exposed to the solar spectrum with an optical power density of 100mW/cm2 for 24 hours. In contrast, the hybrid samples manufactured using as reducing agent Vitis vinífera displayed alterations in C=C (1305 cm-1) bonds, OH from phenolic groups (1408 cm-1, 1164cm-1), and in the substituent group (983 cm-1- 1063 cm-1). For cytotoxicity tests silver nanoparticles were synthesized using gallic acid, and the obtained average size was 18-30nm. The cytotoxicity effect of formulations was evaluated on fibroblasts. The hybrid material was compared with the natural pigments in 1% dimethyl sulfoxide (DMSO) as a photosensitizer for cultures of Streptococcus mutans. The use of silver nanoparticles showed a photoinactivation of bacterial biofilms.

Resume : In order to increase the implant-bone compatibility, a titanium/poly(methyl methacrylate) (PMMA) composite sandwich material with bone-like mechanical properties has been developed [1]. The grafting of PMMA on the Ti surface has been realized by a structuring alkaline treatment prior to the covalent bonding of a phosphonic acid derivative containing a polymerization initiator. The PMMA polymer brush has been then grown from the modified titanium surface via controlled radical polymerization (ATRP). Using high temperature and pressure, a sandwich composite Ti/PMMA/Ti has been obtained by the addition of an intermediate PMMA foil between two Ti/PMMA foils prepared previously. Due to their high efficiency, electron beam (EB) irradiation has been foreseen to achieve sterility of the implant. Therefore samples have been irradiated with three doses 25, 50 and 100 kGy and the mechanical properties of sandwich composite have been evaluated and compared with the starting material. After cutting by a cross section polisher, the cross profile of the sandwich has been observed by MET in order to detect the effects of the EB irradiation on the Ti/PMMA/Ti sandwich. [1] M. Reggente, P.Masson, C.Dollinger, H.Palkowski, S. Zafeiratos, L. Jacomine, D. Passeri, M. Rossi, N. E.Vrana, G. Pourroy and A. Carradò; ACS Appl. Mater. Interfaces 10, 5967-5977 (2018)

Resume : The activation of the mechanotransduction signaling pathways in the cells through the application of magnetic forces and magnetic nanoparticles (MNPs), known as “magnetic actuation”, has been reported to affect the cell phenotype in several ways, especially by inducing stem cell differentiation towards the osteogenic lineage, and by enhancing the organizational complexity of endothelial cells during the development of vascular networks.[1-3] Through this principle, biomaterials and their properties can be designed to act as true fate regulators of stem and other progenitor cells, eventually leading to important advances in the conventional techniques of tissue engineering. The stromal vascular fraction (SVF) is a potent primary co-culture system derived from adipose tissue that contains heterogeneous cell populations including mesenchymal stem cells and vascular progenitors.[4] Here, we generated and described novel MNP-dispersed hydrogels to stimulate SVF cells and obtain constructs for bone tissue engineering with enhanced osteogenic and vasculogenic potential. Magnetic gels were obtained by co-assembly of Polyethylene glycol (PEG)-based hydrogels with PEG-coated superparamagnetic iron oxide nanoparticles (SPIONs, 10 nm of hydrodynamic radius) and freshly isolated SVF cells (6.0×106/ml). Gels were cultured either in the presence or in the absence of osteogenic differentiation factors, and stimulated for 2 weeks by an external static low intensity magnetic field, generated by 50 mT neodymium magnets applied under the culture wells. Gels cultured in the absence of magnetic actuation served as negative controls. The release rate of the SPIONs from gels was determined by quantifying the iron in the culture supernatant (reading of absorbance at 435 nm). Biological characterization of gels was carried out by conventional histological or immunohistochemical imaging of sections, protein and gene expression analysis of osteogenic and vascular markers, and genes acting as key regulators of the mechanotransduction signalling pathways. The tridimensional vascular architecture was studied by confocal microscopy. Finally, following the in vitro stimulation, the gels were then transplanted subcutaneously in immunodeficient mice, and the bone formation and vascularization were histologically analysed after 1 and 8 weeks in vivo. After homogeneous assembly, the SPIONs migrated unidirectionally through the gel texture following the magnetic gradient, and after 14 days, the amount of iron found in the supernatants almost matched the initial amount used for the gel preparation. Cells seeded onto the magnetically actuated gels displayed an equivalent proliferation rate with respect to non-stimulated controls, but also a more frequent elongated phenotype and a higher degree of endothelial structuration. Incremented mineralization was demonstrated by Alizarin Red staining, showing consistent calcium deposits in magnetic gels cultured in the presence of osteogenic factors. However, a mild positivity for this staining was detected even in the absence of osteogenic medium, thus highlighting the osteogenic effects induced by the pure mechanical stimulus produced by the movement of the SPIONs inside the biomaterial. Histological observation also revealed the occurrence of nanoparticle aggregation due to the magnetically controlled redistribution of the nanomaterials. After 1 week of magnetic stimulation, several common osteogenic markers were found overexpressed with respect to control gels cultured into osteogenic medium without magnetic actuation (i.e. Runx2, Col I, Osterix). Coherently to a markedly increased gene expression, also the enzymatic activity of the Alkaline Phosphatase (ALP) was found augmented. After 2 weeks of stimulation, relevant differences were present in the CD31 and α-Sma cell percentage, as representative of endothelial and perivascular populations respectively. Zones of clustering of α-Sma cells, elongated phenotypes and cell alignment in a proto vessel-like architecture were observed only in magnetized gels, whose culture media also contained consistent amounts of VEGF as determined by ELISA at culture day 7. Moreover, the gene expression analysis correlated well by showing stronger activation of endothelial, pericytic and perivascular genes (CD31, SMA, TCAD, NG2, VEGFa). Finally, also genes commonly involved in the mechanotransduction pathways were overactivated, such as JNK1, effector of the classical MAPK pathway. Enhanced vascularization and mineralization were retained in vivo, as demonstrated by increased expression of vascular and osteogenic markers (CD31, BSP, OCN). According to the reported data, we conclude that the exposure of the magnetized gels to a static magnetic field activates panels of osteo and vasculogenic marker genes, showing gross phenotypic signatures such as increased mineralization degree, and more structured and complex endothelial organization. The present biomaterial retains a considerable potential for the future development of innovative tissue interfaces dedicated to efficient bone tissue engineering strategies. [1]. Santos L.J., et al. Harnessing magnetic-mechano actuation in regenerative medicine and tissue engineering. Trends Biotechnol. 2015, 33, 471-9. [2]. Yun H.M., et al. Magnetic nanocomposite scaffolds combined with static magnetic field in the stimulation of osteoblastic differentiation and bone formation. Biomaterials. 2016, 85, 88-98. [3]. Sapir Y., et al. The promotion of in vitro vessel-like organization of endothelial cells in magnetically responsive alginate scaffolds. Biomaterials. 2013, 33, 4100-9. [4]. Saxer F., et al. Implantation of stromal vascular fraction progenitors at bone fracture sites: from a rat model to a first-in-man study. Stem Cells. 2016, 34, 2956-2966.

Resume : Simple and lithium-doped biological-origin hydroxyapatite (Li:BHA) layers were synthesized by Pulsed Laser Deposition and the role of doping reagents on the physical-chemical, mechanical and biological properties of the structures was studied. Morphological examination of coatings evidenced the fabrication of rough surfaces, ideal for the good adhesion of cells and anchorage of implants in situ. Structural investigations demonstrated a monophasic apatite-like nature of the synthesized structures. Compositional analyses revealed the presence of typical natural doping elements of bone, along with a quasi-stoichiometric target-to-substrate transfer. The bonding strength values obtained for the coatings were found to be higher than the threshold imposed by ISO standard regulating the load-bearing implant coatings. After only three days of immersion in simulated body fluid, FTIR spectra showed a remarkable growth of a biomimetic apatitic layer, indicative of a high biomineralization capacity of the coatings. The Li:BHA films elicited improved wettability properties, which could foster rapid bone regeneration. In vitro cell viability tests showed that lithium-doped structures promoted the hMSC growth on film surfaces. Our findings suggest that incorporation of lithium into BHA coatings should provide a delivery system able to promote and even accelerate osseointegration, together with an improved anchorage of bone metallic implants for future biomedical applications.

Resume : Bacterial infections are most prevalent cause for healthcare associated infections (HAIs). One of the common approach to overcome this prevailing issue is development of antibacterial surfaces. Antimicrobial peptides (AMPs), due to their broad-spectrum activity against bacteria and minimal bacterial resistance responses, can be immobilized onto desired surfaces to prepare such antibacterial surfaces. To this end, we covalently immobilize a custom-designed peptide, CKLR (CKLLLRLRKLLRR) on glass substrate to generate peptide-tethered surface. Herein, we describe use of clean-dry technique, UV-Ozone to generate reactive hydroxyl moieties on glass surface. The glass surfaces are, then, selectively functionalized with silane and cross-linker to immobilize CKLR. Each functionalized steps are subjected to biophysical characterizations including elemental composition, surface topography, wettability, and peptide segregation. Further antibacterial efficacy of peptide-tethered surface is determined using colony forming unit assay and anti-biofilm assay. The immobilized CKLR shows significant reduction in viability of Escherichia coli upon interaction, indicating that the designed peptide and tethering strategy are an effective way of creating antibacterial surfaces.

Resume : Antibacterial activity of MXene (Ti3C2Tx), a layered transition metal carbide, is investigated by theoretical model and molecular dynamics (MD) simulations. MXene is an atomically thin two- dimensional material, and we recently showed that it has antibacterial activity toward both of gram- positive and -negative bacteria using scanning electron microscopy and transmission electron microscopy coupled with lactate dehydrogenase release assay.[1] However, the atomistic process of antibacterial activity of MXene was not revealed even though it is a crucial step for understanding the mechanism. Therefore, we investigate the dynamic interaction between cell membrane and MXene nanoparticle, and calculate the free energy of membrane rupture via phospholipid extraction induced by the contact between MXene nanoparticles and biological cell surface.[2] We employed steered MD simulations for guiding the extraction of phospholipid, and measured the free energy profile with Jarzynski equation using eight independent trajectories of phospholipid extraction. We also calculated the free energy profile of phospholipid extraction induced by graphene oxide and compared the results. We believe that our simulations would be a significant contribution for designing a new bactericidal materials based on MXene for water treatment and biomedical applications. [1] K. Rasool, M. Helal, A. Ali, C.E. Ren, Y. Gogotsi, K.A. Mahmoud, "Antibacterial Activity of Ti3C2Tx MXene", Acs Nano, 10 (2016) 3674-3684. [2] O.S. Lee, G.C. Schatz, "Computational Simulations of the Interaction of Lipid Membranes with DNA-Functionalized Gold Nanoparticles", Biomedical Nanoetechnology: Methods and Protocols, Methods in Molecular Biology, Humana Press, 729 (2011) 283-296.

Resume : In the framework of the European project TEXTOS, which aims to develop an innovative 3D matrix for tissue engineering acting as a growing medium of agro-sourced natural polymers for cellular therapy. The originality of this project lies in a two-component scaffold, biocompatible and porous, obtained by a knitting process and ready for use. The base material of this knitted scaffold consists of a PLGA based (poly-lactic-co-glycolicacid) substrate providing the mechanical strength and an "amine rich" surface coating intended for its bio-functionalization. The contribution of amine bonds through the Cyclopropylamine (CPA) which is a promising non-toxic monomer recently used for the deposition of amine-rich thin films for tissue engineering applications. In order to ensure good adhesion of these bonds as a surface coating on the PLGA substrate, a cold plasma treatment is provided for the incorporation of the amine bio-functional groups by CVD technique. Hence, the stability of the deposited CPA depends on the cold plasma parameters: power, monomer flow rate and the discharge configuration. In this work, the influence of the these parameters for the deposition of CPA will be studied from the mechanical point of view (stability and coating cohesion) as well as the biologic one by studying the behavior in cell culture.

Resume : The development of neural interface devices is of considerable interest in the field of biointerfacing engineering including biosensors and bioelectronics, where mechanically soft and low impedance characteristics are required for an efficient electrode-tissue interaction. Conducting polymers including poly(pyrrole) (PPY) and poly(3,4-ethylenedioxythiophine) (PEDOT) have gained attention for microelectrode devices due to 1) excellent biocompatibility, 2) soft mechanical properties, and 3) ability to create materials with well-controlled structures. We reported a new templating method for fabrication of aligned conducting polymer nanotube (ACPN). The structure of ACPN can be precisely modulated to control the electrical properties including impedance and charge-transfer capacity (CTC). The fabrication of ACPN involves 1) electrospinning of monodisperse and aligned PLLA fibers on gold electrodes; 2) electrochemical polymerization of PPY and PEDOT around the PLLA fibers for various polymerization duration and 3) dissolution of PLLA fiber to form ACPN. We found that the impedance of bare gold at 1kHz (282.13±19.71Ω) was significantly reduced with electropolymerization of PEDOT nanotube (41.87±1.55Ω) and PPY nanotube (58.04±3.42Ω). Also, the CTC of bare gold increased from 0.32±0.03mC.cm-2 to 4.86±0.24 mC.cm-2 and 16.3±1.5 mC.cm-2 for PEDOT and PPY nanotubes, respectively. The ACPNs have potential application in the field of bioelectronics, biosensors and drug delivery systems.

Resume : to be announced

Resume : Biodegradable implants such as vascular grafts are new promising therapeutic biomedical substitutes to restore the functions of diseased organs. In order to monitor the location as well as the postoperative degradation degree using magnetic resonance imaging (MRI), magnetic nanoparticles (MNP) were incorporated in the material of the implants and used as contrast agents. The visualization of the degradation process is linked to the question of how the immobilized and clustered MNP in the implant change the MRI signal. For the assessment of these changes, the behaviour of MNP incorporated in polylactic-co-glycolic acid (PLGA) implants as well as of MNP dispersed in different phantoms were analysed with MRI. The phantoms consisted of either free dispersed or immobilized MNP with different sizes and clusters to mimic their immobilization in PLGA implants during the degradation process. Various degrees of MNP immobilization were realized by incorporating them in hydrogels with different meshes sizes. T2- and T2* relaxation time maps of the implants and phantoms were determined to illustrate the local susceptibility differences in each pixel in the cross section of the implants and phantoms. To conclude, the relaxation times of both phantoms and implants were clearly dependent on MNP size, clustering and the degree of immobilization. These results demonstrate the feasibility of quantitative imaging of the degradation degree of implants in vivo with MRI.

Resume : Designing biocompatible polymer-based nanoparticles has become central in the field of theranostic nanoparticles. A current challenge is the development of simplified approaches with improved properties compared with existing methods in terms of biodegradability, toxicity and processing. Currently, there are very few methods allowing the efficient synthesis of particles made of biomacromolecules especially proteins. In coll. with the Univ. of Melbourne (Prof. F. Caruso), we pioneered an original approach using isobutyramide (IBAM) grafts to assemble non-covalently, protein-based hollow capsules and particles without the need of an additional cross-linking or other adjuvant. The process consists in a single adsorption of proteins onto silica templates prealably grafted with IBAM groups or derivatives (e.g., bromoisobutyramide, BrIBAM) followed by template removal[1]. The driving force is attributed to strong H-bonds between the IBAM interface and the polypeptide chains of the proteins. We applied this method to design bioresponsive hollow capsules and particles made of a range of proteins, including enzymes, insulin and human serum albumin.[2] Furthermore, such carriers were shown to release chemotherapeutic drugs upon biological stimuli e.g. through protease degradation or reductive mimetic cytosolic conditions.[3] This approach was also demonstrated for the design of ca. 100 nm size multifunctional protein-based NPs displaying simultaneously delivery of silencing RNA (siRNA) to cancer cells and magnetic resonance imaging (MRI) by grafting gadolinium complexes.[4] In recent works, we translated this innovative protein nanocoating approach for the design of novel hybrid nanoplatforms made of magnetic cores covered with a mesoporous silica shell. Our aim was the design of new systems for MRI [5], magnetic hyperthermia and drug delivery ensured by alternating magnetic field [6]. The nanoplatforms were loaded with antitumoral agents (doxorubicin), and covered by a tight HSA shell to ensure biocompatibility, stealthiness, biodegradability and efficient encapsulation of DOX. The efficient drug release of such HSA-coated core-shell NPs theranostic NPs in protease media mimicking intracellular lysosomes was shown via enzymatic HSA shell biodegradation.[7] The approach was also translated to carbon nanotubes as core systems for drug release response upon NIR light.[8,9] [1] D. Mertz, P. Tan, Y. Wang, T. K. Goh, A. Blencowe, F. Caruso, Adv. Mater. 2011, 23, 5668-5673. [2] D. Mertz, J. Cui, Y. Yan, G. Devlin, C. Chaubaroux, A. Dochter, R. Alles, P. Lavalle, J. C. Voegel, A. Blencowe, P. Auffinger, F. Caruso, ACS Nano 2012, 6, 7584-7594. [3] D. Mertz, H. Wu, J. S. Wong, J. Cui, P. Tan, R. Alles, F. Caruso, Journal of Materials Chemistry 2012, 22, 21434-21442. [4] D. Mertz, C. Affolter-Zbaraszczuk, J. Barthes, J. Cui, F. Caruso, T. F. Baumert, J.-C. Voegel, J. Ogier, F. Meyer, Nanoscale 2014, 6, 11676-11680. [5] X. Wang, X., D. Mertz, C. Blanco-Andujar , A. Bora, M. Ménard, F. Meyer, G. Giraudeau, S. Bégin-Colin, S. RSC Adv. 2016, 6, 93784−93793. [6] D. Mertz, O. Sandre, S. Bégin−Colin, Biochim. Biophys. Acta BBA - Gen. Subj. 2017, 1861, 1617–1641 [7] M. Ménard, D. Mertz, C.Blanco-Andujar, F. Meyer, S. Bégin-Colin, submitted. [8] V. Fiegel, S. Harlepp, S. Bégin-Colin, D. Bégin, D. Mertz, Design of protein-coated carbon nanotubes loaded with hydrophobic drugs through sacrificial templating of mesoporous silica shells, Chem Eur J.,2018, in revision. [9] C. Wells, O. Bringel, V. Fiegel, S. Harlepp, B. Van der Schueren, S. Begin-Colin, D. Bégin, Mertz D., Engineering of mesoporous silica coated carbon based materials optimized for an ultra-high doxorubicin payload and a drug release activated by pH, T and NIR-light. Adv. Funct. Mater 2018, in revision

Resume : Biological processes leading to tissue formation during embryonic development are characterized by large ‘robustness’, namely stability and reproducibility of events. Also regenerative medicine approaches could be more repeatable and effective if they targeted the recapitulation of molecular pathways typical of tissue development. Within the exemplifying context of cartilage and bone repair, this lecture will introduce and discuss the challenges and opportunities of regenerative concepts based on mimicking developmental processes. Rather than engineering a tissue, the strategy would target the use of cells to engineer temporally staged processes, recapitulating events of development. The product would be a construct containing the necessary and sufficient cues to autonomously remodel into the target repair tissue upon grafting. In this perspective, however, cells in adults may strongly differ from multipotent embryonic cells, and typically reside in an environment, which is tightly regulated by post-natal mechanical conditioning or immune/inflammatory processes. Thus, shouldn’t tissue regeneration strategies be inspired by development but adapted to be effective in a context, which is different from the embryo? This would require to re-design the developmental machinery for regenerative purposes by establishing artificial events or conditions. Will the resulting approach of ‘developmental re-engineering’ offer a chance for enhanced tissue regeneration?

Resume : Chemotherapy seeks to minimize tumor progression and increase patient survival. However, the main problem is to find a balance between the drugs therapeutic effect on cancer cells and their deleterious effect on healthy cells. Due to their high hydrophobicity or rather their high hydrophilicity, these molecules must be injected in high and frequent doses, to avoid a rapid elimination and overcome their lack of specificity. Unfortunately, the high chemotherapeutic doses have side effects that patients find difficult to tolerate. Additionally, the diagnosis and imaging of tumor evolution remain a challenge. In order to overcome the challenges associated with chemotherapy, our research group is engaged in developing smart and responsive drug nanocariers. In this talk, I will be discussing two types of drug delivery systems based on iron oxide nanoparticles. Two different approaches will be presented. The first relies on the surface modification of the nanoparticles with an organic macrocycle (cucurbit[7]uril) which allows the adsorption of a drug such as Doxorubicin. The second strategy makes use of mesoporous iron-oxide nanoparticles as nanocarriers. The efficiency of both systems in vitro and in vivo will be discussed. Moreover, the possibility of these two systems to combine chemo and thermal therapies will also be presented.

Resume : Microbubbles are studied as contrast agents for ultrasound imaging, targeted drug, gene and oxygen delivery.[1-3] The shell of the microbubbles is built from lipids, polymers, nanoparticles, or combinations of those.[4, 5] We report stable fluorocarbon-stabilized microbubbles with a phospholipid shell that incorporate dendronized iron oxide nanoparticles. We investigated Langmuir monolayers of mixtures of phospholipids with dendrons fitted with pegylated chains.[6] We found that the dendrons form microdomains within the monolayers (compression isotherms and AFM after transfer). Fluorocarbon gases, when introduced in microbubbles act as osmotic agents[7] and as cosurfactants to phospholipids.[8, 9] We show that introducing the fluorocarbon in either the gaseous or aqueous phase of microbubble dispersions strongly impacts their size and stability.[10] We also obtained small (2-4 µm) and stable (half-life: 1-2 h) microbubbles with dendronized iron oxide nanoparticles (optical microscopy, static light scattering and acoustical attenuation method). 1. J. R. Lindner, Nat. Rev. Drug Disc., 2004, 3, 527. 2. S. R. Sirsi, M. A. Borden, Adv. Drug Deliv. Rev., 2014, 72, 2. 3. M. P. Krafft, J. Fluorine Chem., 2015, 177, 19. 4. S. Sirsi, M. Borden, Bubble Sci. Eng. Technol., 2009, 1, 3. 5. P. N. Nguyen, G. Nikolova, P. Polavarapu, G. Waton, L. T. Phuoc, G. Pourroy, M. P. Krafft, RSC Adv., 2013, 3, 7743. 6. Dendrimers in Nanomedecine, D. Felder-Flesch (ed.), Pan Stanford, Singapore, 2016. 7. E. S. Schutt, D. H. Klein, R. M. Mattrey, J. G. Riess, Angew. Chem. Int. Ed., 2003, 42, 3218. 8. C. Szijjarto, S. Rossi, G. Waton, M. P. Krafft, Langmuir, 2012, 28, 1182. 9. M. P. Krafft, Biochimie 2012, 94, 11. 10. D. Shi, X.-H. Liu, M. P. Krafft, Soft Matter, 2018, submitted.

Resume : In the present study, hybrid surface engineering techniques consisting of DC-sputter deposition (of Ti-6Al-4V) followed by nitriding (by plasma nitriding and plasma ion implantation) have been adopted for improving the wear resistance of AISI 316L stainless steel substrate. Followed by sputtering and nitriding, a detailed characterization of the surface (in terms of microstructure, phases and bond strength), and its mechanical properties (nano-hardness, Young’s modulus and coefficient of friction) have been carried out. The microstructure of the sputtered Ti-6Al-4V consists of very fine particulates of  in the form of clusters. Plasma nitriding and nitrogen ion implantation of the sputter deposited titanium lead to formation of ultra fine white precipitates of titanium nitrides dispersed in the α matrix. The adhesion property of the coating has been evaluated through nano-scratch testing. An enhancement in bond strength has been observed after nitriding which is attributed to nitride formation and with a maximum adhesion strength observed due to ion implantation because of a higher depth of penetration of nitrogen and finer nitride formation. The maximum improvement in Nano-hardness and Young’s modulus after nitrogen implantation is due to the presence of nitrogen in solid solution and formation of nitrides. Keywords: AISI 316L stainless steel, Ti-6Al-4V, sputtering, nitriding, ion implantation.

Resume : The continuous growth of nanotechnology has brought challenging innovations in the synthesis of multifunctional nano-objects for medicine, able to revolutionize the field of diagnosis and therapy. Today’s aim is to develop multifunctional theranostic (i.e. including therapeutic and diagnostic functions) nanoparticles (NPs) which can both identify disease states and deliver therapy and allow thus following the effect of therapy by imaging. Lots of efforts are focused on iron oxide NPs that already demonstrated efficiency as biodegradable and nontoxic T2 contrast agent for MRI along a strong potential for treatment through magnetic hyperthermia (MH). Yet theranostic applications are currently limited by the low magnetic properties of usual magnetic NPs, requiring a local injection of large quantities of NPs. One strategy for increasing the magnetic properties of the NPs is to play on their shape to add shape anisotropy, which can also enable cooperative magnetism. Our knowledge in the area of nanoparticles synthesis through thermal decomposition allowed us to successfully synthesize several anisotropic shapes such as cubes, octopods and plates. After fine structural and magnetic properties characterizations, the various NPs were made biocompatible with a Dendron molecule. The effect of the shape on MH and MRI properties has been investigated in solution but also in vitro and in vivo in order to identify the best design of NPs, promising for theranostic biomedical applications.

Resume : The limited response rate to currently available therapies for patients suffering from colorectal cancer (CRC) motivates the development of novel, more effective treatments. A promising therapeutic approach is currently offered by the use of nanoparticle (NP)-mediated drug delivery, allowing the achievement of high concentrations of anti-cancer therapeutics at the target site, while sparing healthy tissues. However, the possibility to assess the NPs’ impact on tumor cells is hampered by the lack of preclinical systems reliably mirroring the complexity of the in vivo tumor microenvironment (TME). Here, a simple, one-pot and reagent-free method for the preparation of human serum albumin (HSA) NPs using high frequency ultrasound was used1. The prepared HSA-NPs showed high stability and biocompatibility. Our results showed that the newly developed HSA-NPs have a diameter of 150 nm, a uniform size distribution and that they are non-toxic. They can be efficiently loaded with 5-Fluorouracil, a conventional chemotherapeutic drug extensively used in CRC treatment. Our results showed that at early time-point (5 days) HSA-NPs were rapidly accumulated in the stromal component instead of within tumor cells. However, after 24 h of incubation, the HSA-NPs were completely internalized by both the cell fractions. In addition, the HSA-NPs can be efficiently perfused through an in vitro engineered tumor tissue able to mimic the interaction between malignant and non-transformed cells of the TME. The HSA-NPs might be an innovative drug-delivery system, and their delivery efficacy could be tested in a controlled fashion by exploiting the perfusion-based bioreactor TME in the in vitro model. 1. Francesca Cavalieri, Enrico Colombo, Eleonora Nicolai, Nicola Rosato, Muthupandian Ashokkumar, Mater. Horiz., 2016 ,3, 563-567

Resume : Introduction Recent advancements in nanotechnology now also set the stage for improvements in the clinics. CTCs are considered to be of high clinical relevance to diagnose disease and monitor treatment. The molecular profiling of CTCs may allow to uncover novel cancer pathways. However, current CTC detection methods are labor and cost intensive, precluding the analysis of CTCs in large patient cohorts. Methods and Results To overcome these limitations, we are developing miniaturized immuno-nanoparticle-based magnetic flow cytometry chips, allowing the swift and low cost detection of CTCs in blood. We show that magnetic biosensing offers key advantages, a direct electronic read-out, and the option to apply the magnetic cell enrichment directly for cell detection. We will present proof of concept data demonstrating the feasibility of magnetic flow cytometry. However, we found that performance of the technology is dependent of the quality of the used antibody-armed ‘intelligent‘ nanoparticles and plasma proteins adsorbing to nanoprobes. Conclusions Collectively, we report that nanoparticle-based magnetic flow cytometry is highly promising for the further development into an easy to use ‘point of care’ diagnostics, allowing the routine detection of CTCs in HNSCC patients’ blood samples. Applying this technology, prospective (multicenter) clinical studies are needed to clarify the value of CTCs as a surrogate clinical marker for HNSCC.

Resume : Over the last 50 years, biomaterials, prostheses and implants saved and prolonged the life of millions of humans around the globe. Today, nano-biotechnology, nanomaterials and surface modifications provides a new insight to the current problem of biomaterial complications, and even allows us to envisage strategies for the organ shortage. In this talk, creative strategies for designing advanced coatings for health will be discussed. Based on plasma surface modification a platform was developed for antibacterial coatings showing stable bactericidal properties over repeated cycles of cleaning, use or sterilization. This platform could be also adapted for grafting biologically active molecules for interfacing biomaterials and medical devices with the living environment mainly composed by cells and tissue. The importance of grafting versus adsorbing will be discussed considering the molecular weight of the molecules and their biologically activity. Finally, results of in vitro tests with human cells and blood will be discusses, and new strategies for innovative quasi-in-vivo in vitro models from 3D regenerative medicine with human cells will be overviewed.

Resume : The search for new alternatives to antibiotics, with novel mechanisms of action to combat microbial resistance, has become of utmost importance. Herein, we report on the successful fabrication of antimicrobial peptides based nanoparticles through laser-based strategies. The nanovectors have been delivered to implant surfaces as coatings using Matrix Assisted Pulsed Laser Evaporation (MAPLE) that allowed for accurate and precise thickness control, preservation of the chemical integrity of antimicrobial function, physicochemical integrity, and compatibility with non-contact masking techniques. Preliminary characterization of the coatings included SEM, TEM, and XRD in order to check the coating uniformity, nanoparticle shape and cristallinity, comparative chemical investigation of the target and coatings by FTIR to verify functional group and bonding, and adherence tests at the substrate-nanocoatings interface. The antimicrobial activity has been assessed on planktonic and biofilm embedded Gram-negative bacilli resistant strains and the inhibitory activity was quantified by measuring the density of liquid cultures or number of viable biofilm cells. Also the biocompatibility of the obtained nanovectors will be reported. Our studies indicate that antimicrobial peptides based nanoparticles prepared by MAPLE may be used to impart antimicrobial activity to implants, medical devices, and other contact surfaces.

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Resume : Electrical stimulation has been widely used to promote neural activity, such as growth, differentiation, and axonal regeneration of neurons and stem cells, primarily through the extracellular methods of thin film electrodes. To trigger these cellular responses, extracellular application requires unnecessarily high electrical current and potential due to interference from external sources such as cell membrane resistivity and capacitance as well as culture medium. Here, we demonstrate a novel intracellular electrical activation platform to enhance neuronal differentiation of human neural stem cells (hNSCs) by utilizing a vertical nanowire electrode array (VNEA). The vertical NW electrodes pierced the cell membrane without compromising cell viability, and deliver electricity intracellularly, excluding the cell membrane resistivity and capacitance as factors for influence a cell’s effective stimulation. The intracellularly stimulated hNSCs underwent accelerated neuronal differentiation at high efficiency to produce neuronal cells with mature phenotypes and improved electrophysiological functionalities. These results suggest that use of intracellular activation for neuronal differentiation can efficiently generate functional neuronal cells for cell replacement therapy of neurodegenerative disease.

Resume : Copper has been widely accepted as a promising antibacterial surface due to the release of copper ions, although the state of copper surface itself during the release process is seldom mentioned. Therefore in the first part of this talk, we will focus on the chemical changes on the copper surface, from a corrosion standpoint. The corrosion products of pure copper surface were characterised through Raman spectroscopy and scanning electron microscopy (SEM). These products were correlated with the surface antibacterial efficiency against E. coli as well as the ion release level, which is measured by inductively coupled plasma mass spectrometry (ICP-MS). Not only have our results shown the dependency of corrosion products on the physiological environments, they also indicate that these corrosion phenomena indeed affect the antibacterial efficiency obtained from the copper surface. In the second part, similar characterisations basing on copper-containing co-sputtered thin films will be mentioned. These results emphasise the importance of comprehending copper related surface’s antibacterial effects in a corrosion perspective. To conclude, their major significances in interpreting results from antibacterial tests or leading to relevant applications will be discussed.

Resume : Accumulation and formation of unwanted materials (fouling) causes’ loss of function on any given active implantable electrode which has a significant impact in the area of medical implants. Therefore, prevention of fouling from biological materials (bio-fouling) within the implant environment is critical to maximize the functional lifetime of the implant. Effectively interfacing electronic devices with the body depends upon establishing a ‘clean,’ low noise electrical connection so that electrical information can be transmitted (i.e. stimulation) and/or received (i.e. sensing) with high fidelity, sensitivity and resolution. The biggest obstacle to the efficient transaction of electrical information between the electronic and biological systems remains the bio-fouling of implanted electrodes that form an electrical insulation barrier. Our studies using Lubricin (LUB), a mucin-like glycoprotein, as an anti-fouling surface coating on metal electrodes demonstrated an impressive ability for LUB to self-assemble on electrode surfaces rendering them non-adhesive to blood serum proteins and major proteins of the extracellular matrix. In addition, the self-assembled LUB coating demonstrated no detrimental impact upon the electrical performance of the electrode (as evaluated via electrochemical techniques). The work to be presented will highlight these highly desirable properties of LUB and discuss the implications these have in the development of implantable electrodes.

Resume : Surface micropatterns are being extensively studied for their important impact on cell-material interaction, as they can be used to control cell behavior, such as orientation, size, adhesion and division. As a result, the use of conventional microfabrication techniques, especially soft lithography borrowed from the microelectronic industry, have drawn tremendous interest in bioengineering and biotechnology. Thus far however, while these techniques allow creating precise textures on planar substrates, it remains a challenge to fabricate micropatterns on curved and confined surfaces. Here, we report a simple and scalable surface patterning method based on preform-to-fiber thermal drawing to generate sub-micrometer patterns on flexible polymer fibers and ribbons. Patterns of various sizes and shapes were realized on the external surface of flat ribbons or on the highly-curved internal surface of hollow-core fibers made out of thermoplastic, biocompatible or biodegradable polymers. To highlight the potential of this technique for bioengineering and biotechnology, we present two applications: patterned ribbons were used to control the alignment and elongation of stem cell growth, and patterned hollow-core fibers were used as a nerve guidance conduit for Dorsal Root Ganglia (DRG). This novel fabrication technique offers unique opportunities in bio- and neural engineering, both in the context of in vitro studies and in vivo regenerative strategies. [Adv.Func.Mater. 1605935 (2017)].

Resume : Prevention of pathogen colonization of medical implants is a major medical and financial issue since infection by microorganisms constitutes one of the most serious complications after surgery or critical care. Immobilization of antimicrobial molecules on biomaterial surfaces is an efficient approach to prevent biofilm formation. The deposition of polyelectrolyte multilayers through the layer by layer method (LBL) has stimulated a large number of studies aimed to understand the physicochemical mechanisms responsible for the self-assemblies and toward the development of numerous applications among them in biomaterials field. The buildup of polyelectrolyte multilayers occurs through the alternate dipping of a substrate into polyanionic and polycationic solutions. To use them as coatings for biomedical devices, we developed a new kind of biocompatible films based on polysaccharides built by alternate or simultaneous spraying process. We reported also a self-defensive coating against both bacteria and yeasts where the release of the antimicrobial peptide is triggered by enzymatic degradation of the film due to the pathogens themselves (Figure 1). Biocompatible and biodegradable polysaccharide multilayer films based on functionalized hyaluronic acid (HA) by cateslytin (CTL), an endogenous host-defensive antimicrobial peptide, and chitosan (CHI) were deposited on a planar surface. The films fully inhibit the development of Gram-positive Staphylococcus aureus bacteria and Candida albicans yeasts, which are common and virulent pathogens agents encountered in care-associated diseases. Furthermore, the limited fibroblasts adhesion on (HA-CTL-C/CHI) films, without cytotoxicity, highlights a medically relevant application to prevent infections on catheters or tracheal tubes where fibrous tissue encapsulation is undesirable. Refs: 1. Cado G. et al. Self-defensive biomaterial coating against bacteria and yeasts: polysaccharide multilayer film with embedded antimicrobial peptide. Adv. Funct. Mater (2013) 23, 4801. 2. Cado G. et al. Polysaccharide films built by simultaneous or alternated spray: a rapid way to engineer biomaterial surfaces. Langmuir (2012), 28, 8470.

Resume : In this study, 22 amino acid length synthetic peptide that corresponds to ADP-5 region of amelogenin has been investigated for its periodontal regenerative potential in vitro, by using human primary gingival fibroblast and mouse cementoblast (OCCM.30). The effect of ADP-5 at the concentration of 200-50-10 μg/mL on cell adhesion and spreading were tested for both types of the cells. After 24h, the cells were fixed and stained with Phalloidin-FITC and propidium Iodide. Flouresence microscopy images of the cells have shown that they adhere and spread in the presence of corresponding concentration of amelogenic peptide. Proliferation of the cells were screened by Alamar Blue assay on Day1, 3 and 7 at concentrations 1/5/10/50/200 μg/mL. The amount of fluorescence was measured which corresponds to the number of living cells and their metabolic activity. ADP-5 did not show an inhibitory effect on cell growth when compared to control. Osteogenic potential of cementoblast was determined by Alizarin Red S staining. This test is commonly used to identify calcium deposition during osteocytes differentiation. Cementoblasts were grown in the presence of only ADP-5 (200 μg/mL and 100 μg/mL) or ADP-5 was included into osteogenic differentiation medium. After 10 days of treatment synergistic effect (ADP-5+osteogenic medium) on calcium deposition was observed. Collectively, the results revealed that synthetic peptide has great potential for the periodontal regeneration.

Resume : Materials for advanced wound healing are of great interest for both physiological and aesthetic reasons, with a societal and economic impact of the pathological wound healing impairment that can occur in aging-related diseases such as the diabetic foot and venous ulcers. Hyaluronic acid (HA) is currently used in tissue regeneration either alone or conjugated with bioactive molecules and/or nanoparticles [1-3]. Silver (Ag) and gold (Au) nanoparticles have intrinsic potential therapeutic effects in the wound healing, in terms of antibacterial and anti-inflammatory actions, respectively [4]. In this work, HA at low (i.e., 200 kDa) and high (i.e., 700 kDa) molecular weight, respectively with pro- and anti-angiogenic properties, have been investigated in the interaction with spherical gold and silver nanoparticles of size in the 10-50 nm range. UV-visible and NMR spectroscopies, AFM and QCM-D have been used to scrutinise the plasmonic and conformational features, the morphology and the viscoelastic properties of the hybrid HA-Ag and HA-Au systems, respectively. Proof-of-work experiments with fibroblast cells have been performed with proliferation tests and confocal imaging, with the use of a fluorescent HA derivative. [1] Neuman, M.G. et al., 2015, J Pharm & Pharmac Sci, 18, 53. [2] Sciuto, S. et al., 2015. PCT/IB/2015/055782. [3] Anisha, B.S. et al., 2013. Int J Biol Macromol, 62, 310. [4] Di Pietro, P. et al., 2016. Curr Top Med Chem, 16, 3069.

Resume : The internalization of an adsorbed particle by a cell can be strongly hindered as compared to particles moving freely in a culture medium. The adhesive force can indeed oppose forces that cells such as macrophages can develop during phagocytosis for example. But the uptake of adhered particles might also be hindered due to the presence of the substrate or neighboring particles that can restrain the membrane wrapping at the basis of the cellular internalization processes. It thus appears that it is of fundamental interest to evaluate to which extend the cellular uptake is hindered by this adsorbed state. Here we examine the stability of model particle-based monolayers built with silica particles ranging from 35 nm to 450 nm, and exposed to murine macrophages. This stability, associated to the ability of the macrophages to internalize adsorbed particles, is discussed on the basis of scanning electron microscope observations, as a function of the particle size and incubation time. Our results demonstrate that particles larger than 200 nm are almost fully removed by the cells, whereas smaller sizes show a remarkably higher stability, with a surface density of particles remaining on the substrate that increases with decreasing the size of the particles. Additionally, we have observed that the damaging process is characterized by an induction time that increases with decreasing the particle size, suggesting a particle size-dependent time window for which the monolayer is stable.

Resume : The self-assembly of lipids were widely studied for many biomedical applications, such as drug delivery, gene therapy and protein crystallization. In this study, we focus on using the charged disc-shaped bicelles to form complexes with the Bovine serum albumin (BSA). The disc shaped bicelles are formed by mixing long-chain lipids with short-chain lipids at suitable ratios. In the experiment, we used charged bicelles doped by DC-Cholesterol, DOTAP. Two types of bicelles, DPPC/diC7PC and DPPC/CHAPSO, were used in this study. The doping charge percentages were varied while the BSA concentration was fixed at 0.115 mM. The complex structure was investigated by using the synchrotron small-angle X-ray scattering beam line 23A at the NSRRC, Hsinchu, Taiwan. Due to the strong charge interaction, the BSA induces bicelle to form aggregates. In the presence of BSA, the DPPC/CHAPSO/DOTAP bicelles form clear lamellar structures at the charge doping percentage 5% or higher. At 30% charge doping percentage or higher, the lamellar diffraction peaks splits into two sets of peaks, indicating formation of more complex phases or structures. As for the DPPC/CHAPSO/DC-cholesterol/BSA system, it also forms lamellar structure but the single lamellar phase turns into more complex phases at just 20% charge doping percentage. As revealed by the TEM pictures, the bicelles form stacking structures in the form of fused sheets. These large lamellar stacks also aggregate into large bar shaped structure. The DC-cholesterol system needs to reach a higher charge doping percentage to induce the structural changes as compared with the DOTAP system. The cationic charge of DC-Cholesterol is buried deeper in the hydrophilic head group layer of the bilayer and it is less effective in attracting the BSA as compared with DOTAP. The cationic charge of the DOTAP head group is on the outer region of the hydrophilic head group layer and the electrostatic attraction with BSA would be much stronger.

Resume : A stretchable, biocompatible strain sensor for monitoring bladder fullness to treat various urological conditions Stuart HANNAH and Marc RAMUZ We present a fully biocompatible, soft, stretchable sensor device, capable of monitoring dimensional changes/stretch of the bladder wall. Our implantable sensor is used to determine bladder fullness, without the need for complex and invasive surgical procedures used currently, enabling the development of new treatment options for various urological conditions, including OAB and urinary urge incontinence. The sensors comprise thermally evaporated Cr/Au thin films (~ 150 nm) on compliant, stretchable polyurethane (PU) film (≤ 50 µm), arranged in a ‘dogbone’ design produced by laser patterning, with sensor W and L dimensions on the mm scale to produce sensitive resistive sensors. We demonstrate repeatable sensor response up to 50% stretch with almost no hysteresis, with sensitivity ~20 Ω/mm (W=0.5, L=6mm). The sensors have also been tested in vitro on an isolated pig bladder, subjected to repeated filling and emptying cycles to mimic natural bladder behaviour. Sensors were attached strongly to the bladder surface using a biocompatible hydrogel adhesive. As bladder volume changes, the sensor changes resistance as a function of stretch, and displays very good repeatability over several bladder filling/emptying cycles. Our soft, stretchable, biocompatible sensors pave the way for fully implantable health monitoring systems of the future.

Resume : Several years ago, we have shown that strong deformations of cancerous cell bodies can be obtained when osteosarcoma cells are cultured on micropillared substrates and that these alterations also affect the nucleus shape. These strong deformations of cells and of their organelles which don't affect viability and proliferation draw an analogy with the metastatic process. That is why the understanding of cells mechanics and of the related inner forces in this model is essential. Here, we analyse the nuclear deformation on micropillared surfaces of cancer cells. As the deformability of cells is strongly connected with their cytoskeleton dynamics, we combine live imaging and AFM elasticity measurements with treatment with inhibitors of cytoskeleton and LINC complex molecules to decipher the involvement of each cytoskeleton component in the nucleus deformation. In parallel the kinetics of deformation of cancer cells on micropillars is analysed in relation with the chromatin condensation. Our findings confirm that actomyosin microfilaments associated with intermediate filaments and LINC molecules play a major role in this deformation. Microtubules are not always involved depending of the cell type. We also demonstrate that pulling down forces imparted by the cytoskeleton are necessary to promote deformation by changing the chemistry on top or in between interpillar space of pillars by spin coating cell adhesive (PnBA) and repellent polymers (PDMAA).

Resume : Drug delivery vehicles/devices are promising candidates for the delivery of pharmaceuticals and biopharmaceuticals mainly because they ideally augment aspects such as targeted delivery rate of internalization, therapeutic efficiency and perhaps also minimize toxicity effects of the loaded drug. The development and establishing the safety of novel drug vehicles is a tedious and challenging process with one of the primary challenges being that a single device should be able to encapsulate a diverse array of chemical and biological compositions. These compositions can consist of either hydrophobic, hydrophilic or amphiphilic structures and should be easily encapsulated in sufficient quantities. Moreover, the vehicles have to be adaptable so that they can sequester the aforementioned wide array of chemical compositions using, in principle, a relatively trivial methodology. The delivery devices should also have safety, patient and regulatory compliance and should also be resilient to a variety of denaturing conditions, and it would also be beneficial that these devices should be amenable to surface functionalization so that they can be exploited for targeted delivery. Currently, a large amount of research is being devoted to fabricating new drug delivery vehicles; however, one of the important mitigating factors has been always the biocompatibility issue. As such, in the biomaterial literature the chemical compositions that have been actively pursued can be classified into two conventional categories: Organic and Inorganic. In the organic class, a large portion is occupied by a sub-class of structures consisting of polymers. Polymeric materials such as PEG and PLGA are perhaps the most common chemical structures that are routinely used in research and in commercial products due to their FDA approval. Analogously, studies have also been reported to support the drug delivery potential of inorganic structures, but these have been limited in number. The limitation arises because of three main aspects: Initially, the chemical composition has to be inherently biocompatible, as such researchers are restricted to working with stoichiometries such as calcium carbonate (CaCO3) and a very specific type of calcium phosphate namely hydroxyapatite [Ca10(PO4)6(OH)2][22]. However the inorganic chemistry does not lend itself easily to forming hollow or reticulated structures of these chemical compositions. Therefore the second difficulty associated with the use of inorganic structure for drug delivery is the manipulation of the overall morphology to yield ideally a porous internal cavity. Finally, the last impediment is the size of the ensuing device. There are a wide range of sizes of nanostructures that have been reported in the literature that work efficiently as drug delivery vehicles. In principle, it can be generically stated that idealized structures less than 200 nm in diameter appear to perform well with in vitro and in vivo assays. Due to these aforementioned factors, researchers have actually opted to work with chemical compositions such as; SiO2, Au, Ag, Fe2O3, etc. as their chemistry lends easily informing hollow nano-sized spherical structures that could be potentially be viable for drug delivery. However, as these are not inherently non-toxic, therefore extensive bioassays have to be done to determine the long term biocompatibility of such nanostructures. Presented here is a study on a material that circumvents the above hurdles. Herein a systematic study on the drug delivery efficacy of novel HAp hollow nanotubes is presented and their behaviour has been shown in comparison to the oft-cited spherical, dense nanoparticles of HAp. Hence a novel parameter has been exploited wherein the morphology is manipulated from a spherical structure to a 1D hollow nanotubular shape for drug delivery. The talk will detail: (A) single-particle analysis showcasing XRD, SEM, TEM, SAED, EELS, EDS and BET measurements to prove the sole formation of HAp hollow nanotubes, (B) the biocompatibility assays and internalization study of these tubes in presence of cell lines such as RN46A Neuronal cells, L929 Mouse Fibroblast cells, Primary skin cells, Hela cells and MG63 Osteoblastoma cells, (C) comparison of these two structures for encapsulation capability using molecules whose composition has been varied from being hydrophilic to hydrophobic along with varying their molecular weights upto 70kDa and (F) a comparative study of nanotubular vs. spherical morphology showcasing their loading capacity using a Paclitaxel and Doxirubicin as model cargos, the release/retention study showing improved rates for the ID structures and cell internalization will be quantitatively detailed from Imaging Flow Cytometry. Most importantly, the mechanism of cellular uptake of spherical vs 1D hollow tubes will be compared.

Resume : Key Words : bioactive surfaces, bioactive polymers, grafting technique, adhesive protein, host response, Despite the fantastic progresses in biomaterials science due to the improvements in macromolecular chemistry, biology, materials science and surgical techniques, the failure rate of biomedical implants remains too high. To summarize the causes of these failures can largely be attributed to inadequate control of the biological response to the implant leading to a foreign body response and/or infection. Materials used in the field of implantable medical devices have to exhibit properties of “perfect compatibility” to the living systems to become “biointegrated”, i.e. accepted by the host. However, such perfection is extremely hard to achieve. The compatibility of an implantable material in the fully operant biological context is directly related to its structural and surface properties and also requires an understanding of the biology of the surrounding tissues. The mechanisms underlying implant failure have to be better understood: this is the constant objective of biomaterials research. Amongst those mechanisms, the protein/surface interactions represents one of the most important since the adsorption of proteins is the very first event to occur when a material is implanted into living tissue [1-3]. The functionalization of polymers and surfaces to make them bioactive is the starting point in controlling the protein/surface interactions which dictate events that follow and may lead to integration or failure of the implant. Failure can involve infection and/or the foreign body response mounted by the immune system of the host [4]. Various strategies have been employed to control protein adsorption including the synthesis of polymers bearing chemical groups capable of modulating the biological response or the functionalization of implant surfaces using those same functional groups to create bioactive surfaces suitable for implant. These strategies are exemplified by the optimization of bioactive polymers to control the adsorption of cell adhesive proteins for target tissues such as bone and ligament tissues [5-15]. For those both applications, the outcomes demonstrate that the competitive protein binding behaviour which occurs at the protein-surface interface makes a significant contribution to cellular responses observed both in vitro and in vivo. REFERENCES 1. Anderson JM et al. Biomaterials. 1984 5(1):5-10. 2. R. A. Latour et al. Encyclopedia of Bioamterials and Biomedical Engineering 2005 3. Ratner B. D. J Cardiovasc Transl Res. 2011 4(5):523-7. 4. El Kadhali, et al. Biomacromolecules 2002 3(1) : 51-56 5. 4. Latz C, et al. Biomacromolecules. 4:766-71, 2003. 6. Michiardi A, et al. Acta Biomater. 6:667-75, 2010. 7. Viateau V et al. Arthroscopy. 2013 ;29(6):1079-88 8. Vaquette C et al. Biomaterials. 2013;34(29):7048-63. 9. Felgueiras H et al. Langmuir. 30:9477-83, 2014. 10. Zorn G et al. Langmuir 2011 27(21):13104-12. 11. Rohman G et al. J Mater Sci Mater Med2015.. 26(7):206. 12. Chouirfa H et al. RSC Advances 2016 6 (17), 13766-13771 13. Felgueiras H et al. Appl Mater Interfaces. 2016; 8:13207-13217. 14. Chouirfa H et al. Appl Mater Interfaces. 2018; 10:1480-1491 15. Felgueiras H et al. Journal of Colloid and Interface Science 2017; 491: 44-54

Resume : Hollow organosilica nanoparticles incorporating amino group with uniform size are described. These nanoparticles were successfully prepared via microemulsion method. Additionally, this new nanohybrid structure with a cationic charge were loaded with two anti-cancer drugs, gemcitabine hydrochloride or methotrexate. The effect of the nanoparticle structure on the drug delivery impact of the two anti-cancer drugs was studied in vitro with MCF-7 breast cancer cells.

Resume : Cells have evolved specific sensing mechanisms to recognize and integrate a diverse set of environmental cues. Here we report a new cellular sense which we term “curvotaxis” that enable the cells to read and integrate cell-scale curve topographies, a ubiquitous trait of natural environments. We develop sinusoidal 3D surfaces presenting continuous variations of cell-scale curvature, and monitored cell behavior on these simplified biomimetic landscapes. We found that cells avoid convex regions during their migration and position themselves in concave valleys. Computational modeling and live imaging suggest that curvotaxis relies on a dynamic interplay between the nucleus and the actin network - the nucleus acting as a mechano-sensing organelle that drives cell migration. Further analysis show that substratum concavity increases nuclear sphericity, lowers cellular tensions and down-regulates a subset of genes involved in stem cell differentiation. All together, this work identifies curvotaxis as a new guiding mechanism and suggest that cell-scale topography might be a true component of the stem cell niche.

Resume : Nanoemulsions (NEs) are clear, transparent and homogeneous mixtures of oil and water stabilized by surfactant(s). Due to their unique properties, such as long-term kinetic stability, high drug solubilization capacity, low interfacial tension, and low viscosity, NEs are widely used in food, cosmetics, and pharmaceutics. Chlorambucil (CBL) is an antineoplastic nitrogen mustard used in the treatment of chronic lymphocytic leukemia, Hodgkin's disease, and others. It alkylates and crosslinks DNA, resulting in disruption of DNA function, cell cycle arrest and apoptosis. In the present work, we have designed and synthesized a ?-amino acid derived surfactant, sodium N-dodecanoyl-?-amino butyrate (SDGAB) bearing fatty acid chain. We have optimized the process and preparation of D-limonene-in-water NE compositions using a catanionic mixture of SDGAB and cetyltrimethylammonium chloride (CTAC) surfactants. The NEs have small droplet size in the range 35-70 nm as revealed by light scattering experiments. Effects of surfactant and oil content have been investigated in terms of droplet size. The NEs have excellent stability over a temperature range of 25-50 oC and an ageing period of 6 months. The NEs have shown high solubilization capacity for CBL. At slightly acidic pH (5.5), the droplet size grows substantially and the system becomes highly polydispersed. Thus, they could be used in pH-triggered release of CBL.

Resume : Surface topography and chemistry represent the major issues in cell-surface interfaces dictating the biological reactions. Laser based techniques can be used in synergy with materials properties to engineer controlled and tunable interfacial characteristics of various bio-surfaces for in vitro cell -material interaction studies. This work presents the production and characterization of biosurfaces and biomaterials with well-defined hierarchically patterned topographies processed by laser methods (e.g. Pulsed laser deposition, Matrix Assisted Pulsed Laser Evaporation-MAPLE, and direct laser ablation/texturing) used to screen various mammalian cell behavior. For example, the characteristics of crystalline pyramidal nanostructures of ceria CeO2 obtained by PLD were correlated to early response of osteoblast cells. Moreover, the cells grown on Ceria pyramidal patterns exhibited significantly enhanced focal adhesion development, aligned cytoskeletal morphogenesis, and osteogenic differentiation compared to cells on flat substrates. Other examples envisaged various surfaces obtained by MAPLE, which were modified with different polymers (PEG-PCL) or biocompounds (Lactoferrin, Cisplatin) to obtain thin films with multiple functionality, from protein repelling characteristics, to antitumoral activities and smart coatings. Direct ablation of ceramics was utilized to create topographical features as physical guidance structures. These structures allow the controlling of cell adhesive or guidance areas. Nevertheless, PDMS replica starting from laser processed surfaces were used for in vitro studies as models for silicone implants or for hepatocite like cells differentiation, the regulated expression of the DsRed reporter proved a valuable tool not only for rapid screening of novel cell growth substrates favouring cell differentiation We illustrate the potential of the laser based technologies with examples ranging from ceria based coatings to textured zirconia ceramics or soft scaffolds to be used in biomedical studies. Acknowledgments. This work was supported by Romanian National Authority for Scientific Research (CNCS – UEFISCDI), under the projects PN-II-RU-TE-2014-4-2434 and Nucleu Program.

Resume : A lack of inexpensive, simple, specific and mild cell recovery methods is one of the factors impeding the development of methods to culture clinically relevant numbers of therapeutic stem cells. Enzymatic cell detachment (Trypsin) is the industry standard technique for therapeutic cell recovery. Trypsinization has many short comings including being derived from animal/human pancreatic enzymes, considerable expense, and the cleaving of cell surface proteins leading to dysregulation of cell function, inducing apoptosis in cells when exposed for longer time period. There are a number of non-enzymatic solutions for cellular detachment available, however these methods show only moderate efficiency and are generally unsuited for scale up to clinically relevant volumes. Thus scalable alternatives are required. Surface-plasmons generated by irradiating surface bound gold nanostructures with near infra-red light can mediate non-toxic cell detachment. In collaboration with St. Vincent’s Hospital, Melbourne Australia we are developing new gold nanorods based coating for 2D substrates and 3D microbeads, in order to develop biomaterials suitable for cell recovery on a clinically relevant scale. We have shown that strongly adherent fibroblast cells undergo efficient photothermal (plasmonic) cell detachment from substrates functionalized with gold nanorods. Furthermore, the detached cells are unharmed and can be re-cultured. Our further research has shown that this protocol is equally applicable to mesenchymal stem cells (MSC) and their multipotency is maintained throughout the detachment process. We have also demonstrated that plasmon induced surface detachment does not effect the MSC to differential into either adipose or cardiac cell types and thus presents a very promising approach to non-enzymatic harvesting of stem cells.

Resume : PolyHIPE is porous polymeric materials from polymerization of high internal phase emulsion (HIPE) which contains 74% of internal phase (disperse phase) and 26 % of external phase (continues phase). Typically, polyHIPE was prepared from styrene (S) and divinylbenzene (DVB) and they were used in various kind of applications such as catalyst support, gas adsorption, separation membranes, and tissue engineering scaffolds due to high specific surface areas, high porousity, ability to adsorb large quantities of liquid. In this research, cellulose from water hyacinth (Eichornia Crassipes), an aquatic plant that grow and spread rapidly in rivers and waterways in Thailand, was added into polyHIPE to increase mechanical property of polyHIPE. Addition of unmodified and modified cellulose to poly(S/DVB)HIPE resulting in an decrease in the surface area and thermal stability of the resulting materials. Mechanical properties of the resulting polyHIPEs filled with both unmodified and modified cellulose exhibited higher compressive strength and Young’s modulus by 146.3% and 162.5% respectively, compared to unfilled polyHIPEs. The water adsorption capacity of filled polyHIPE was also improved.

Resume : Controlling the alignment of anisotropic nanoparticles within three-dimensional (3D) environment over large-scale is rather big challenge. A facile method to align rod-like nanoparticles in 3D hydrogel environment by shear flow in large-scale was developed. The hydrogel precursor solution flow was chosen to provide unidirectional shear force to control the direction of alignment of nanoparticles, while the orientated structures of nanoparticles can be quickly fixed through the fast transition of sol-gel of hydrogel. The degree of orientation of the aligned structure as well as the distance between the nanoparticles can be regulated by adjusting the concentration of the hydrogel and virus nanoparticles. Both repulsion interaction and shear flow contribute synergistically to the assembly process. This technique does not require the application of strong magnetic or electric fields, nor does it require the use of specialized lithography. We believe this novel method can be used to fabricate inorganic-organic composites including inorganic anisotropic nanoparticles and will have potential applications in tissue engineering, sensing, electronic and optical fields

Resume : Carbon and silicon play both a key role in all living organisms, one as a part of organic compounds and the other as a trace element, thus their biocompatibility does not need to be questioned, however, it depends on the doses. Silicon carbide nanoparticles (SiC-NP) of diameter around 2-5 nanometers and with different surface terminations (as prepared, -OH terminated and -NH2 terminated) were fabricated, characterized and tested with respect to different human cell types. Cell lines of osteoblasts, and monocytes were used to establish possible application and provide inside into their interactions. Firstly, the cytotoxicity of each type of particles was tested by gradually increasing the concentration of nanoparticles administered to cells by measurement of their metabolic activity and its changes in dependence on time, dose and cultivation conditions (presence or absence of protein corona on nanoparticles). Secondly, cell death occurrence and its type was observed by detection of lactate dehydrogenase in the supernatant (necrosis – accidental death) and activated caspases in cells (apoptosis – programmed death). By combining these results the influence of surface termination and its importance in respect to biological systems can be seen.

Resume : The development of materials for the treatment of bone defects and diseases is a topic that is nowadays drawing a great deal of attention. Among synthetic materials, injectable bone cements hold an important position and are currently used in minimally invasive surgery. In this field, the poorly investigated Mg phosphate-based cements (MPCs) display many attractive features that, in some cases, make it possible to overcome the drawbacks associated to the deeply studied calcium phosphate cements. However, the different preparation conditions reported in the literature make it difficult to assess MPCs properties and to identify the optimal preparation conditions. This contribution deals with the investigation of MPCs prepared by mixing tri-magnesium phosphate (TMP) and di-ammonium hydrogen phosphate (DAHP). The effects of the powder to liquid ratio and of DAHP concentration were investigated. The cohesion and the setting time of the pastes were studied, and the crystallinity of the final material was determined by means of X-rays diffraction. The morphology and the microstructure of the cements were analysed with electron microscopy, while gas sorption was used to examine surface area and pore size distribution. This multi-technique approach allowed us to relate the amount of formed crystalline material with the properties of the cement, to hypothesise a mechanism of formation and to identify the preparation conditions to be used to obtain a cement with the desired features.

Resume : In the work as the substrate functional scaffold for the cell culture were prepared from the animal aortic valve. The protocol for acquisition fragments of tissue has been developed. Properly crafted tissue was subjected by the acellularization process, which means the removal of cells from the tissue in order to obtain pure, non-degraded extracellular matrix. Elimination of cells from the tissue was carried out by unconventional methods of materials science involving a laser ablation with different power and beam configuration and acoustic waves with different frequencies. Physical processes were designed to cause the elimination of tissue cells. The issue of the cell elimination from tissue, and then formation of new tissue on the basis of the extracellular matrix meets strong clinical interest, but at the moment states a complex issue from a scientific point of view.

Resume : The bactericidal properties of most orthopedics implants are not satisfactory and bacteria can adhere onto the surface cause serious problems such as infections. Nanoparticles can be incorporated to kill bacteria but some of the more potent ones have toxicity in large quantities. A new strategy to prevent biofilm formation on implants is surface nanopatterning. In this work, a nanopatterned polymeric surface is fabricated from silk using colloidal masks and reactive ion etching (RIE). The Silk plate is used as a substrate and fabricated according a protocol based on the Bombyx mori cocoons. The silk plate is spin-coated with a solution containing polystyrene nanospheres with a colloidal mask followed by RIE to perform nanopatterning. The staphylococcus aureus (S. aureus) bacteria are cultured on the samples and the bactericidal activity is assessed by live/dead staining and fluorescence microscopy. By adjusting the etching time, the effects of the height and lateral distance between the nanocones on the bactericidal behavior of the samples are studied and the optimal height, aspect ratio, and spacing between nanocones are determined. Keywords: Bactericidal activity, silk, plasma treatment, colloidal mask

Resume : Stem cell therapy has long fascinated researchers and patients because of the possibility of treating a disease by counteracting or replacing it at its genetic roots. The use of stem cell sources that avoid ethical concerns, such as adipose-derived stem cells (ADSCs), may enable practical stem cell treatment. Achieving precise manipulation of these cells will maximize the potential benefits of stem cell therapy. Here, the multifunctional concept of using defined matrix/interface modifications to support stem cell culture is demonstrated to provide synergistic coupling with concurrently immobilized FGF-2 and chitosan, and the resulting cell culture matrix/interface enables the proliferation of spheroids of ADSCs with augmented stemness in the form of self-renewal and enhanced (trans-)differentiation potential for diversified cell lineages in the mesoderm, endoderm and ectoderm. The modification and the co-immobilization are performed using a straightforward one-step vapor-based coating technology applicable to a wide range of cell culture materials. The concurrent immobilization of FGF-2 and chitosan revealed an important prospective for designing a material interface that confirms that effective and sustainable factors to determine stem cell fate are obtainable using a facile multicomponent modification approach on culture substrates.

Resume : Electrospinning, an electrostatic fiber fabrication technique has evinced more interest in recent years due to its versatility and potential for applications in diverse fields especially in tissue engineering which represents a very promising area.1 Polycaprolactone (PCL) polymer has been approved for biomedical application and offers excellent mechanical properties and slow biodegradation, making it an appropriate material for use as a scaffold for tissue engineering2-4 for the regeneration of different tissues.5-10 To overcome the PCL hydrophobicity which leads to a lack of favorable cell response, a common tissue engineering approach is the conjugate of bioactive molecules onto the scaffold surfaces in order to enhance cell attachments, proliferations and differentiation on the scaffolds. Previous studies carried out in our laboratory have shown that the grafting of polymers or copolymers bearing anionic groups such as sulfonate, carboxylate and phosphonate can favor cell adhesion and differentiation.11-13 We have been working on this issue to develop a new PCL functionalized14 electrospun implant that can be used as a GTR (guided tissue regeneration)15 membrane to aid the effective regeneration of defective periodontal tissues in periodontitis.16 This study shows the elaboration of different PCL membranes, the appreciation of mechanical behavior to observe the impact of the structure and functionalization and compares the effects on the in vitro biological response. References 1 N. Bhardwaj, et al., Biotechnology Advances, 2010, 28, 325-347. 2 D. Li, et al., Biointerfaces, 2014, 21, 432-443. 3 A. P. Tiwari, et al., Colloids and Surfaces A : Physiochem. Eng. Aspects, 2017, 520, 105-113. 4 B. D. Ulery, et al., J Polym Sci Part B : Polym. Phys., 2011, 49, 832-864. 5 P. Plikk, et al., Biomacromolecules, 2009, 10, 1259-1264. 6 P.M. Mountziaris, et al., Biomaterials, 2010, 31, 1666-1675. 7 J. W. S. Hayami, et al., J. Biomed. Mater. Res:A , 2010, 92, 1407-1420. 8 C. Vaquette, et al., J. Biomed. Mater. Res. A, 2010, 92, 1270-1282. 9 D. R. Nisbet, et al., Biomaterials, 2009, 19, 30, 4573-4580. 10 H. Chen, et al., Int. J. Biol. Macromol., 2011, 48, 13-19. 11 F. El Khadali, et al., Biomacromolecules, 2002, 3, 51-56. 12 F. Anagnostou, et al., Biomaterials, 2006, 27, 3912-3919. 13 G. AMOKRANE, et al., IRBM, 2017, 38, 190-197. 14 G. AMOKRANE, et al., Materials Science & Engineering C, submitted Dec 2017. 15 G. SAM, et al., Journal of Clinical and Diagnostic Research, 2014, 8, ZE14-ZE17. 16 C. Vaquette, et al., Biomaterials, 2012, 33, 5560–73.

Resume : Titanium, and its alloys are widely used for the development of biomedical implants due to their high strength, remarkable biocompatibility, resistance to corrosion, conduciveness to osteointegration etc. The tissue-titanium (implant) surface interactions are fundamentally important in assessing the functionality of the implants. Kelvin probe is a non-contact and non-destructive technique to measure the surface work function of the metals; even after the measurement, the surface remains virgin in the Kelvin probe technique. The surface work function is very sensitive to any charge transfer process from proteins (a major constituent of tissues) to the surface of the metals. In the present study, piranha solution cleaned Titanium surfaces (10 mm x 10 mm) are immersed in different sized proteins: (i) lysozyme (14 kDa), (ii) carbonic anhydrase (30 kDa), (iii) bovine serum albumin (66 kDa) and (iv) human immunoglobulin (150 kDa). The surface work function of the virgin, and protein treated Titanium surfaces have been studied. The surface work function results show substantial evidence of surface modification of Titanium with the proteins. Even after thorough washing steps, the protein dipped Titanium surface shows a permanent modification. Results are being analysed to correlate the protein concentration to the surface modification.

Resume : Medical hydrogels have been gaining widespread interest. Several properties like hydrophilicity, chemical modification and compatibility are of desire to adjust them for specific applications. These hydrogels can consist of various different polymers including Carrageenans and Furcellaran. Usually these latter compounds find use in the food processing industry but are also being surveyed for oral application of medical active substances ([2]), as cell embedding media besides possible uses in skeletal regeneration of bone and cartilage ([4]). Older studies of Carrageenans reported anti-inflammatory, anti-coagulating, anti-viral potential as suppression of the immune response ([5]). Carrageenans, extracted from red algae, provide means for physically bound hydrogels. Gelling is best described by the domain model ([1]) where the amount of added binding ions is crucial. Gel-forming types are Kappa- and Iota-Carrageenan which have different ionic selectivity. Kappa gels with several ions but, constraining to a physiological system, best with Potassium to result in strong and brittle gels. Iota-Carrageenan in comparison is gelled, again physiological, best with Calcium ions producing more elastic and soft results. Blends of Kappa and Iota-C. are extensively used in food industry combining positive properties of the two compounds, as Iota-Carrageenan also shows higher acid resistance. Furcellaran has an equivalent structure to kappa-Carrageenan but involves a smaller amount of sulphate groups. It likewise is reported to form stable, brittle and strong gels with Potassium ions. Carrageenans and Furcellaran cannot be gelled in vivo, which somehow limits possible medical application. Gel structures need production prior to insertion in vivo. However, gels can be formed by Potassium and Calcium, which enables extended variety in gel design. Potassium levels in most physiological fluids are higher than Calcium levels. There is limited data on stability of Carrageenan gels in vivo, as they are used in scaffolding applications where relatively fast degradation is desired, followed by substitution of the gels by native human tissues. Several studies report the loss of gel stability due to the loss of physical crosslinking ions. Gels are instable in an ion-equilibrium state with its surrounding. Ion exchange processes will destabilize and degrade gel structure and mechanical instability will result. Weakening of the gels will eventually lead to complete gel dissolution. For possible long-term applications of the gels, stability in ionic solutions and physiological fluids is of special interest. Several mid to long-term applications of the compounds are imaginable. This research is focused on whether ionically equilibrated stable gels are possible at ionic concentration in human tissues. Dependant on the targeted tissue, different physiological fluids are present. Neglecting the protein - and cell content, the influence of enzymes and other contents in the fluids, one can investigate the influence of primary ionic species on the gels. Several physiological fluids are imaginable and presented research has, among others, focused on blood plasma. Ionic concentration values, for the most gel influencing species in blood plasma, are reported for Sodium (142 mM), Potassium (5 mM), Chloride (103 mM) , Calcium (2,5 mM) and Magnesium (1,5 mM). Of the latter two, only a part is present in dissociated form, 1,3 mM and 1 mM respectively ([3]). In blood plasma, concentrations of binding cations are very low and resulting gels suffer from a lack of binding ions. Other fluids with higher ionic content of Potassium enable better the application of long-term stable hydrogels based on ionic crosslinking. For the investigation of mid to long-term stable gels, the author applied an inverse method. The investigation focused on stable gels at physiological ionic concentration. By synthesis of theses gels, conclusion can be drawn which polymer concentration and polymer type can be used. Rheological measurements of Kappa-, Iota-Carrageenan- as Furcellaran-gels have been undertaken. Interim steps were adaption of the base compound prior to gel production, mixing of gels at physiological ionic concentration and rheological analysis of the samples. This included dialysis of Carrageenans and Furcellaran prior to use and ionic content quantification determination by atomic absorption spectrometry of solutions. The investigation solely focused on unitary gels and specification of mixed gels as acidic degradation of them will be part of further investigation. Results: The study leads to the conclusion that stable gels in physiological fluids can be synthesised. At blood-plasma ionic concentrations, the gels had to be highly concentrated. High elasticity of Iota-Carrageenan gels was found and is expected to be beneficial for applications in tissues with high mechanical strain. Dialysis was necessary to adapt certain ionic levels of gels. Industrially extracted algal compounds usually contain vast amounts of ionic species. Despite careful planning, it was impossible to correctly adjust all ionic concentrations to physiological levels in the gels. Sodium or Chloride levels were in excess in several gels, and their influence on the gels could be determined. Future investigation will focus on long-term stability of given fluids. This includes considering possible physical variations in ionic constituents levels as addition of proteins, amino acids as other compounds. [1] Edwin R. Morris, David A. Rees, and Geoffrey Robinson. Cation-specific aggregation of carrageenan helices: Domain model of polymer gel structure. Journal of Molecular Biology, 138(2):349–362, April 1980. [2] J. Necas and L. Bartosikova. Carrageenan: a review. Veterinarni Medicina, 58(4):187–205, 2013. [3] Ayako Oyane, Hyun-Min Kim, Takuo Furuya, Tadashi Kokubo, Toshiki Miyazaki, and Takashi Nakamura. Preparation and assessment of revised simulated body fluids. Journal of Biomedical Materials Research Part A, 65A(2):188–195, 2003. [4] Marcia T. Rodrigues, Pedro P. Carvalho, Manuela E. Gomes, and Rui L. Reis. Biomaterials in preclinical Approches for Engineering Skeletal Tissues. 2015. [5] A.W. Thomson and E.F. Fowler. Carrageenan: a review of its effects on the immune system. Agents and Actions, 1981.

Resume : Herbal extracts represent a rich source of bioactive compounds, use in recent years, in pharmaceutical nanotechnology. To improve therapeutic management, a number of nano-encapsulation strategies have been approached, including the obtaining of bio polymer nanoparticles, which have the role of protecting bioactive natural compounds and improving their bioavailability and pharmacological properties. The aims of this study is the obtaing and characterization of chitosan–sodium tripolyphosphate nanoparticles (NPs) charged with Cyperus rotundus L. standardized extract (CrE). The herbal extracts (CrE) have been investigated by UV-Vis spectroscopy for quantitative determination of the total polyphenol, flavonoids and polyphenolcarboxylic acids content, in according with Romanian and European Pharmacopoeia. Bio polymer nanocarrier have been analyzed through UV-vis spectroscopy to identify the nanoparticles fingerprint and dynamic light scattering (DLS) to determine the particle size, polydispersity index and zeta potential. The properties of bio polymer nanocarrier are proved by in vitro pharmacological tests and structural analysis. The viability of cells were detected by MTS - assay that emphasize significant stimulation of the growth of mouse fibroblast 3T3 and human monocyte SC in a dose-dependent manner. Antioxidant properties was studied using the chemiluminescence technique and DPPH(2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay. In addition Atomic Force Microscopy (AFM) reveal a specific topography of bio polymer nanocarrier. Keywords: bio nano-carrier systems, herbal extracts, chitosan, antioxidant activity, cells viability

Resume : The skin on a chip is one of the studies that has attracted attention because it can be used to screen the toxicity and efficacy of certain materials including cosmetics, skin detergents, and drugs by various limitations of animal experiments such as the ethical and regulatory issues and the considerable difference between animals and human. For this reason, we investigated the in vitro three dimensional vascularized skin on a chip to mimic the structures and functional responses of the human skin using collagen/fibrin hydrogel(CFH) for dermis and poly(l-lactide-co-caprolactone)(PLCL) nanofibrous electrospun membrane(NEM) for the epidermis. To mimic vessels, we created channels in the CFH and coated with human umbilical vein endothelial cells(HUVECs). Consequently, we could find that channels coated with HUVECs formed a vessels-like structure, and microvascular networks were formed in CFH like the dermis. Moreover, it was confirmed that PLCL-NEM formed the epidermis like structure. Our results suggest that the vascularized skin-on-a-chip model can potentially be used for testing the toxicity of cosmetics or drugs by three-dimensionally simulating the native human skin structure.

Resume : Modern two-dimensional nanomaterials can be successfully used in biovisualization as quantum dots, in targeted delivery of drugs, phototherapy, biosensorics, and as promising antibiotics. In the past few years, the interest in two-dimensional nanomaterials based on transition metal trichalcogenides has been increasing, in particular, on zirconium trisulphide nanoplasts, which have extraordinary optical properties. However, no studies of the biological effects of this material have been conducted so far. For this study zirconium trisulfide (ZrS3) nanoribbons or nanosheets were prepared by chemical vapor transport method (CVT) by the reaction between zirconium metal powder and sulfur in vacuum sealed quartz ampoule. Then we analyzed the effect of freshly prepared, 2-hour and 24-hour water colloidal solutions containing 0.001 ... 1 g/l of zirconium trisulphide (ZrS3) nanoribbons with genetically modified photobacteria strain E. coli. We report that fresh solutions of ZrS3 at all concentrations stimulate the activity of bacteria. The maximum luminescence of bacteria was noted with 1 g/l suspension of ZrS3 nanoribbons, exceeding the control values by 5 times. Two-hour colloids had a stimulating effect only in the maximum concentration - the luminescence indices were 2 times higher than for the control samples. In case of 24-hours suspensions, inhibition of bacterial activity was observed, and as the concentration increased, the luminescence of E. coli decreased - at 1 g / l, the value was 3 times lower than the control. The identified effects are probably related to the gradual degradation of ZrS3 nanoribbons and the release of H2S into the solution, which protected the bacteria against oxidative stress at low concentrations, and at high levels it was toxic. The results of the study can be used in the development of nanoscale devices based on ZrS3 nanoribbons for biomedical applications.

Resume : Electrospun polymer fiber scaffolds can support biological cell growth due to the similarity to the extracellular matrix (ECM) and has been reported for the application of tissue engineering for many years[1]. Electrohydrodynamic (EHD) co-jetting is a process developed in our group for creating anisotropic micro- to nanometer-sized polymer fibers for use in the next generation of ‘smart’ devices. Using this economical, scalable and robust technique, polymer fibers with three or even more different compartments can be obtained[2-3]. Additionally, we developed a novel jetting technology that allows the defined orientation of the fibers in 3D architectures[4]. This leads to an orientation of the cultured cells in unique patterns. By combining both techniques, it is possible to integrate biological polymers (e.g. alginate) and ECM molecules (e.g. hyaluronic acid) into the framework structures. Besides, through further manipulation of the surface by functional groups or by incorporation of signal molecules the ECM is mimicked even more precisely. These new material compositions and the orientation of the fibers can modify the chemical and physical properties of the scaffolds, opening a completely new field of drug delivery systems in tissue engineering. [1] G. Kim et al., Biomed. Mat. 2008 3, 025010 [2] S. Bhaskar rt al., J. Am. Chem. Soc. 2009, 131, 6650 [3] S. Bhaskar et al., Angew. Chem. Intern. Edit. 2009, 48, 4589 [4] J. Lahann et al., U.S. Patent Application No. 13/266,377

Resume : According to the immediate progress of material science, different semiconductor materials corresponding to complex metal oxides have shown promise as powerful antimicrobial agents against microorganisms. In this current study, we present non toxic nanomaterials, which prepared by using a simple and effective method and showed considerable promise as antibacterial agents. The α-Ag2WO4 crystals were obtained by coprecipitation method by using different solvents (water, alcoholic solution, and ammoniacal solution). These nanocrystals was structurally are characterized by X-ray diffraction patterns, which show that the newly synthesized α-Ag2WO4 were well indexed to the orthorhombic structure. Two morphologies were observed by field-emission scanning electron microscopy images: microrods in alcoholic solution and flower-like structures in water and ammoniacal solution. The α-Ag2WO4 powders were also characterized by UV-Vis diffuse reflectance spectroscopy and photoluminescence measurements (PL). Our studies demonstrate that the antibacterial efficiency against Candida albicans, the Gram-positive bacteria methicillin resistant Staphylococcus aureus, and the Gram-negative bacteria Escherichia coli, of the α-Ag2WO4 synthesized using alcoholic solution is higher than that of the other samples. This may be attributed to two facts: (i) the a-Ag2WO4 nanorods present a high superficial area compared with the α-Ag2WO4 flower-like synthesized using ammoniacal solution and water. (ii) The ability of α-Ag2WO4 to generate electron-hole pairs is due to intrinsic defects in the form of distortions or vacancies on [WO6] and [AgOx] clusters, that form the α-Ag2WO4. Whens this clusters are polarized, the [WO6]’/[WO6]● or [AgOx]’/[AgOx]● are formed. The polarizeted ([WO6]●), interact with H2O giving rise to OH* and H●. While the [WO6] distorted clusters with e’ excess ([WO6]’), reacts with O2 and generate O2′. Then, the O2′ and H●, newly formed, reacts to forming O2H*. The [AgOx], with vacancies, acts in a similar way. According to the literature, these oxidizing radicals, OH* and O2H*, are the mainly responsible for the bacterial death. For the α-Ag2WO4 nanocrystals synthesized using alcoholic solution has higher amount of [WO6] and [AgOx] distorted clusters, than the α-Ag2WO4 nanocrystals synthesized using ammoniacal solution and water, as observed by UV-Vis and PL spectral deconvolution, as result, more oxidizing radicals are produzed by the α-Ag2WO4 synthesized using alcohol as a solvent, and so, this material has higher antibacterial efficiency than the others.On the basis of these results, we introduce α-Ag2WO4 nanocrystals as a new family of antimicrobial materials for their potential use in water treatment and biomedical applications.

Resume : Design of new osteoinductive biomaterials to recapitulate an optimized physiological environment capable of recruiting stem cells and instructing their fate towards the osteoblastic lineage has become a priority in orthopedic surgery. This work aims at evaluating the bioactivity of BMP combined with human plasma fibronectin (FN/BMP) delivered in solution or coated onto titanium-hydroxyapatite (TiHA) surfaces. Herein, we focus on the comparison of in vitro osteogenic efficacy in mouse C2C12 pre-osteoblasts of three BMP members, namely: BMP-2, BMP-6 and BMP-7. In parallel, we evaluated the molecular binding strength between each BMP with FN using the Surface Plasmon Resonance (SPR) technology. The affinity of BMPs for FN fundamentally differs depending on the BMP considered. Indeed, combining FN with BMP-2 on TiHA surfaces potentiates the burst of gene-mediated osteogenic induction, while it prolongs the osteogenic activity of BMP-6 and surprisingly annihilates the BMP-7 one. These results correlate with FN/BMP affinity for TiHA, since BMP-6 > BMP-2 > BMP-7. Finally, by analyzing the osteogenic activity in the peri-implant environment, we showed that osteoinductive paracrine effects were significantly decreased upon (FN/BMP-6), as opposed to (FN/BMP-2) coatings. Altogether, our results support the use of FN/BMP-6 to develop a biomimetic microenvironment capable to induce osteogenic activity under physiological conditions, with minimum side effects.

Resume : Water-soluble CdSe quantum dots (QDs) were synthesized using four different ratios of Mercaptosuccinicacid (MSA) as the surface capping agent through a one-step process at low temperature T (100°C).The obtained MSA-capped CdSe nanocrystals were characterized regarding their morphology, structural and optical properties.The resulting nanocrystals were synthesized in the cubic structure with a spherical shape as confirmed by X-ray diffraction and transmission electron microscopy.Combining transmission electron microscopy imaging and calculations using UV-visible absorption spectrum and X-ray diffraction pattern, the diameter of the synthesized nanocrystals was estimated for the different ratios. Band structure parameters of the functionalized CdSe QDs with MSA were determined and quantum confinement effect was evidenced by optical absorption,fluorescence and Raman measurements. As perspective of this work, these novel optical properties that must be taken into account when developing any probing applications.

Resume : Thermosensitive polymers have shown great performance in the biomaterials field due to their ability to change in local environment under temperature stimulus. When combined with nanoparticles, they can lead to superior materials with integration of both components properties (flexibility of polymers and mechanical resistance of nanoparticles). In this sense, nanocomposites were prepared by in situ polymerization of the thermosensitive poly(N-vinylcaprolactam) (PNVCL) in the presence of 1 and 5% of mesoporous silica nanofibers (NFS). Rheological properties showed the presence of SiO2 increased up to 2-fold the loss and storage moduli of PNVCL at temperatures above the sol-gel transition (34°C). The investigation of PNVCL/nanocomposites and water interactions during temperature-induced phase transition was elucidated by measurements of 1H spin–spin relaxation times with NMR. They indicated the presence of SiO2 changed the hydration/dehydration profiles and prolonged the release of water molecules during the sol-gel transition. Alamar Blue assay was also employed to verify the nanocomposites cytotoxicity through direct contact with Human MSCs (Lonza) to assess the cell viability after 1 and 3 days. At different concentrations, the materials showed biocompatibility and induce cell proliferation. These outcomes suggest nanocomposites have superior rheological properties than PNVCL, are biocompatible and can be potential thermosensitive systems for biomaterials applications.

Resume : Silver nanoparticles (AgNPs) exhibit unique optical properties, high thermal and electrical conductivity, as well as antibacterial properties. Silver nanoparticles (AgNPs) have been exploited in a wide range of potential applications in medicine, cosmetics, renewable energies, environmental remediation and biomedical devices. The paper present the design, synthesis, physicochemical and biological properties of biohybrids based on silver nanoparticules and standardized plant extracts. The biohybrids based on silver nanoparticules enhanced stability, and also provide a means to deliver greater amounts of target therapeutic via high density surface coverage. They were used Ocimum basilicum L. standardized extracts (ObSE) containing flavonoids, polyphenols and phenolic carboxylic acids. This study reveals the relationship between silver nanoparticles and herbal extracts, and can lead to a new biohybrids with enhanced therapeutic anti inflammatory efficiency. To obtain the AgNPs, silver electrodes with a purity of 99.99% inserted in Type 1 ultrapure water have been used to produce a silver ion solution which was reduced to form nanoparticles. Selfassembling of the silver nanoparticles on ObSE for obtaing the biohybrids was performed by homogenization in the Ultra Turrax Digital High Speed system. The properties of the biohybrids were analyzed through various techniques: the presence and formation of AgNPs by UV-vis spectrometry, the particle size and zeta potential by dynamic light scattering (DLS). In addition the cytotoxicity of the biohybrids tested was determined in vitro using a mouse fibroblast culture line L929 (ATCC CRL-6364) and a human monocyte line SC (ATCC CRL 9855) as an experimental model. Evaluation of the anti-inflammatory effect in vitro was performed by assessing the production of nitric oxide in macrophages stimulated with LPS (lipopoly-saccharides). The results have shown a high anti inflammatory activity for biohybrids suggesting that this type of bio product can be used as potential amplifier of pharmacological properties for a large class of herbal extracts and natural bio compounds. Keywords: silver nanoparticles, anti-inflammatory biohybrids, electrolysis.

Resume : The use of nanocomposite materials can contribute significantly to improve the quality of population life. In this context, Nylon 6 (N6) has been investigated as a bone tissue scaffold and trisodium trimetaphosphate (TMP) can be used as potential candidates for dental applications due to the anticaries action of TMP when present in a biocompatible scaffold as N6. Therefore, the insertion effect of different TMP concentrations in a N6 polymeric matrix was evaluated and correlated to the physicochemical properties of nanocomposites. TMP nanoparticles were prepared by mechanical milling for 48h. N6 and its nanocomposites were prepared by electrospinning technique, while, the N6/TMP nanocomposites were processed by adding 2.5, 5 and 10% w/w (TMP:N6). Scanning electron microscopy images showed the formation of nanofibers in N6 and nanocomposites with ~150 nm of thickness, and the presence of TMP homogeneously distributed over the nanofibers. 13C NMR spectra indicated the same chemical shifts for nanocomposites. Thermogravimetry analyses demonstrated improved thermal stability of N6/TMP nanocomposites with higher TMP concentration according to its barrier effect. Additionally, the increase in the glass transition temperature in N6/TMP nanocomposites indicated the reduction of polymeric chains mobility. These findings showed a new approach to add TMP nanoparticles by electrospinning in a polymeric matrix, forming stable nanofibers with potential application in dental biomaterials.

Resume : The hydroxyapatite enriched with SiC was prepared as possible candidates for biomedical applications especially for implantable devices that are in direct contact to the bone. The coatings were prepared by RF magnetron sputtering on Ti-6Al-4V alloy using pure hydroxyapatite and SiC targets, at different substrate bias values, ranging from -30V to - 75V. The GIXRD, XPS and FTIR analyses revealed the presence of hydroxyapatite structure. The hardness and elastic modulus of the hydroxyapatite were increased by SiC addition. All coated substrates presented good corrosion resistance in SBF solution (pH=7, 37 C). For cell viability and morphological investigations, the plain and coated samples were seeded with osteoblast cells. After 5 days of culture, the cell viability was enhanced on coated Ti-6Al-4V, more evident for SiC enriched hydroxyapatite. The electron microscopy showed the presence of more cells on the surface of SiC-enriched hydroxyapatite than those observed on the surface of the uncoated alloys or plain hydroxyapatite coatings. We acknowledge the support of the Romanian National Authority for Scientific Research and Innovation, project no. 90PED/2017, as well as Core Program 2018.

Resume : Calcium phosphate-based glasses are a unique group of materials that offer potential for use in biomedicine. Based on a modifiable P-O-P network these glasses are bioresorbable, as they react and dissolve in the physiological environment and they are eventually totally replaced by regenerated hard or soft tissue. The degradation rate of these glasses can be controlled from minutes to several months via changing their composition and the breakdown components can be easily metabolised in the body. In this study, porous phosphate-based glasses (PPGs) in the P2O5-CaO-Na2O system were synthesized using the sol-gel route that allows an easy control of their morphology and porosity. We have used the non-ionic block copolymer PluronicP123 as a templating agent to achieve the desired porosity. The structure of the PPGs was characterized using a series of complementary techniques such as scanning electron microscopy (SEM), N2 adsorption surface analysis (BET), X-ray diffraction (XRD), 31P magic angle spinning nuclear magnetic resonance (31P MAS NMR), and Fourier transform infrared (FTIR) spectroscopy. Results indicate that these materials have a great potential for drug delivery and tissue engineering applications.

Resume : The high degradation rate of magnesium alloys is the main drawback to their extensive use, especially in biomedical applications. There is a need for developing new coatings that provide simultaneously degradation resistance and increase the biocompatibility. The development of novel multifunctional hybrid coating based on graphene oxide and hydroxyapatite to enhance adhesion of bone cells and to stimulate its proliferation and differentiation is currently subject of tremendous research interest. Knowing the intrinsic exceptional properties of both graphene oxide (GO) and hydroxyapatite nanoparticles (Hap) it is anticipated that its combination in hybrid coating will promote synergic properties that can be of major impact on bone mineralization. In this work, a struvite coating containing Hap and GO, was applied on AZ31 magnesium alloys by electrophoretic deposition. The obtained coating was them thermal treated at 300ºC to improve the degradation resistance. The physic-chemical properties of the coatings were evaluated by SEM and TEM microscope, RAMAN spectroscopy, X-Ray diffraction. The coated samples were immersed in simulated body fluid solution at physiologic temperature and the coating performance was studied by electrochemical spectroscopy. The results confirmed that the thermal treatment of the coatings slow down the degradation rate of magnesium alloy, especially when hydroxyapatite nanoparticles and graphene oxide were introduced in the coating formulation.

Resume : The improvement in bioactivity of bioglass due to addition of Titania Nanotubes is significant. 45S5 bioglass with 45 wt.%, SiO2 24.5 wt.%, Na2O, 24.5 wt.% CaO and 6 wt.% P2O5 was used. Upon introduction of Ti into the bioglass matrix and, an improvement in strength, bioactivity, nontoxicity, corrosion resistivity and compressive strength was found. This was tested by coating the substrate with hydroxyapatite. The Ti Nanotubes were synthesized by an electrochemical anodization method because of its controllability. Ti alloy samples were anodized in an electrolytic cell with a two electrode system using Cu as counter electrode. The anodized samples were characterized by EDX, FESEM and contact angle measurement instrument. Uniformly distributed titania nanopores were developed. The Ti Nanotubes produced at 30V in 4 hours displayed hydrophilic nature.

Resume : α-Ag2WO4 materials have been intensively studied because of their potential applications in antimicrobial actions. However, a better comprehension of the antifungal action and toxicity of the α-Ag2WO4 toward cancer cells is still needed. In this study, we investigate how the laser irradiation in femtoseconds and electron beam affects these properties, through structural and morphological correlations of these new materials. The materials was synthesized by coprecipitation method and irradiated with electron beam (Ag2WO4:E), and non-focused (Ag2WO4:NF) and focused (Ag2WO4:F) femtosecond laser. The antifungal activity of microcrystals was evaluated against biofilm formation of the Candida albicans. The results obtained by counting colony forming units per mL (CFU/mL) show that the most effective microcrystal was, in descending order: Ag2WO4:F, Ag2WO4:NF, Ag2WO4:E and Ag2WO4. The Ag2WO4. To investigate the in vitro toxicity of the samples, the test was carried out with the cell lines MB49 (tumor cell), BALB/3T3 and L929 (non-tumor cell). Nanotoxicology effects were analyzed to study apoptosis and necrosis processes and reactive oxygen species production. Ag2WO4 irradiated and non-irradiated exhibited a higher cytotoxic against cancer MB49 cells and in some materials, no cytotoxicity the non-cancerous cells, BALB/3T3 and L929. This ability may be of clinical interest because of the effectiveness of α-Ag2WO4 to distinguish between normal and cancer cells in cancer therapy.

Resume : The rational design of self-assembling β-peptides provides great potential for extending the structural diversity of hierarchical assemblies. However, the study of the supramolecular assembly of β-peptides is in its infancy. Herein, we report the supramolecular assembly of β-peptide nanofibers and a helical wrapping phenomenon of these nanofibers on bundled single-walled carbon nanotubes. Previously, the de novo designed “betaVhex” β-peptide was described to form a water-soluble hexameric oligomer. We found that increasing the betaVhex concentration promoted the axial growth of betaVhex hexamers through end-to- end interactions. Interestingly, the betaVhex nanofibers were effectively dispersed CNTs, and electron microscopy revealed that these nanofibers enwrapped CNTs with a variety of helicities. Molecular dynamics simulations of the wrapping trajectories of the betaVhex bundles on a CNT surface confirmed that the helical nanofiber conformations on the CNTs were thermodynamically favorable. Our findings contribute to the current understanding of peptide self-assembly processes and provide opportunities for the design of nanobiomaterials with potential applications in biomedicine.[1-2] [1] One-Sun Lee, Yamei Liu, George C. Schatz "Molecular dynamics simulation of β-sheet formation in self-assembled peptide amphiphile fibers" Journal of Nanoparticle Research 14 (8), 936 [2] Tao Yu, One-Sun Lee, George C. Schatz "Molecular dynamics simulations and electronic excited state properties of a self-assembled peptide amphiphile nanofiber with metalloporphyrin arrays" The Journal of Physical Chemistry A 118 (37), 8553-8562

Resume : Nowadays, one of the main challenges of the medical field still remains the development of a new generation of medical implants with improved characteristics. An efficient solution could be the functionalization of different medical implants by thin biomaterial layers. In this respect, we applied Pulsed Laser Deposition (PLD) technique to obtain hydroxyapatite (HA), bovine derived HA (BHA) and Li doped BHA (BHA:Li) coatings on medical grade Ti substrates. The experiments were conducted in a vacuum chamber using a KrF* excimer laser source (λ = 248nm, τFWHM ≤ 25ns, υ=10Hz). In order to improve stoichiometry and crystallinity, the as-deposited coatings were submitted to a post-deposition thermal treatment in water vapors atmosphere. Specific coating surface morphologies (rough surfaces) were evidenced by scanning electron microscopy (SEM), appropriate for a good cell adhesion. The elemental concentrations of the evaluated materials were recorded by using the Energy Dispersive Spectroscopy (EDS) and showed a quasi-stoichiometric target-to-substrate transfer. The crystalline structure of the coatings was monitored by X-ray diffraction (XRD) and evidenced the presence of a HA phase only. In order to evaluate the biocompatibility of the as-deposited coatings, cellular adhesion, proliferation and differentiation tests were conducted. Taking into consideration the improved performances as compared to synthetic HA coatings, lithium-doped HA layers could be considered as viable materials for future implantology applications.

Resume : The study of tungsten-based materials has drawn attention from the scientific community because of its excellent optical and electrical properties applied in science and technology. The silver tungstate (Ag2WO4) semiconductor is an important multifunctional material that exhibits both physical and chemical properties as: photocatalysis, photoluminescence, gas sensor in addition to the antimicrobial activity against Candida Albicans. The method of preparation of this material; microwave-assisted hydrothermal system stands out for its advantages being a fast method presenting a high yield of the product, of low cost, that presents uniform heating using low processing temperatures below 200ºC. The effect of different times of the synthesis exposed to the microwave at a constant temperature was evaluated and correlated with the physicochemical properties of this material. The Ag2WO4 nanoparticles were prepared by the microwave assisted hydrothermal method at the times of 2.4.8 and 16 minutes at 140 ° C. Scanning electron microscopy images showed that the Ag2WO4 nanorods are better defined according to the increase in the time of exposure to microwaves, in addition to the observation of silver growth on the nanorodes. The UV-vis diffuse reflectance spectra for the The α-Ag2WO4 crystals showed a slight decrease in the time of 2.4 and 8 min for Egap values; while for the 16 min sample there was a greater drop for Egap. Experiments to measure the antifungal activity of α -Ag2WO4 against Candida Albicans were able to inactivate and kill CA cells at a concentration of 0.0725 mg / mL. These findings show us a possibility to explore a broad spectrum of interactions between these complex metal oxides and antimicrobial systems.

Resume : Pure titanium (Ti) is commonly used as implants in dental clinics because of its superior mechanical strength and high corrosion resistance. However, significant mismatch in Young’s modulus of Ti (110 GPa) with that of the bone (30 GPa) produces a “stress shielding effect”, which has been identified as one of the major reason for implant failure. Moreover, Ti doesn’t cover requirements, such as antibacterial ability and real biocompatibility. In fact, bacterial activity can be decisive in the formation of peri-implantitis, which is defined as inflammatory disease that affects soft and hard tissues around dental implants and is characterized by bleeding upon probing and progressive implant failure. Therefore, surface modification of titanium by coatings capable of reduce the mismatch in Young’s modulus and microbial adhesion seems an efficient way to increase the adherence and spreading of cells, taking control of the osseointegration process. Physical vapor deposition offers a magnificent route to develop new -rich Ti coatings, offering an incomparable frame for the combination of metallic elements capable of showing unique physicochemical properties. Goal of this work is to design biocompatible coatings by magnetron sputtering with lower Young’s modulus and with antibacterial properties on polymer substrate. For that, titanium, niobium have been combined with silicon and silver, since silicon is essential in bone formation and bone health and silver is highly effective at inhibiting bacteria growth as it damage their DNA, in order to produce Ti-Nb-Six and Ti-Nb-Six-Agy [0x-15, 0y5 at.%] coatings,. Preliminary results show as Young’s modulus value is lower than 70 GPa and Berkovich hardness value is between 8 and 12 GPa. This combination of high hardness with reduced Young’s modules opens the window to the development of “hard but tough” coatings with superior fatigue resistance and low Young’s modulus capable of minimizing the stress shielding effect, increasing the osseointegration and the useful live of the implant.