Electron microscopy approach to the wetting dynamics of single organosilanized mesopores.

Columnar mesoporous silicon (PSi) with hydrophobic vs. hydrophilic chemistries was chosen as a model for the local (pore-by-pore) study of water-pore interactions. Tomographic reconstructions provided a 3D view of the ramified pore structure. An in situ study of PSi wetting was conducted for categorized pore diameters by environmental scanning TEM. An appropriate setting of the contrast allows for the normalization of the gray scale in the images as a function of relative humidity (RH). This allows constructing an isotherm for each single pore and a subsequent averaging provides an isotherm for each pore size range. The isotherms systematically point to an initial adsorption through the formation of water adlayers, followed by a capillary filling process at higher RH. The local isotherms correlate with (global) gravimetric determination of wetting. Our results point at the validation of a technique for the study of aging and stability of single-pore nanoscale devices.

Exchange bias coupling and bipolar resistive switching at room temperature on GaSb/Mn multilayers for resistive memories applications.

This work present structural, morphological, magnetic, and electrical properties of GaSb/Mn multilayer deposited via DC magnetron sputtering at room temperature and at 423 K. The samples are characterized by forming layers of 3, 6 and 12 periods of the GaSb/Mn structure. Through XRD patterns, it was possible to stablish the formation of GaSb, Mn3Ga, and Mn2Sb2 phases. FTIR measurements present an optical interference associated with periodicity and the homogenous thickness of the layers. HR-SEM shows the multilayer architecture with columnar microstructure in the formation of layers with grain nucleation on the surface. A ferromagnetic-like behavior was observed in the multilayers at room temperature related to the domains and interlayers interaction. Additionally, the hysteresis curves present shifts attributed to the effect of exchange bias coupling. I-V curves show RESET-SET states of the multilayer system with bipolar resistive behavior, which can be modified by external magnetic fields. The resistive switching evidenced corresponds to the conductive mechanism based on the capacitive conductance and the formation of conductive filaments in multilayer structure.

Innovative prolonged-release oral alkalising formulation allowing sustained urine pH increase with twice daily administration: randomised trial in healthy adults.

A multi-particulate fixed-dose combination product, consisting of a combination of two alkalising salts formulated as prolonged-release granules, ADV7103, was developed to obtain a sustained and prolonged alkalising effect. The specific release of both types of granules was shown in vitro through their dissolution profiles, which indicated that potassium citrate was released within the first 2-3 h and potassium bicarbonate up to 10-12 h after administration. The long-lasting coverage of ADV7103 was confirmed through a randomised, placebo-controlled, double-blind, two-period study, measuring its effect on urine pH in healthy adults (n = 16) at doses of alkalising agent ranging between 0.98 and 2.88 meq/kg/day. A significant increase of urine pH with a positive dose-response in healthy adult subjects was shown. Urine pH above 7 was maintained during 24 h with a dosing equivalent to 1.44 meq/kg twice a day, while urine pH was below 6 most of the time with placebo. The effect observed was non-saturating within the range of doses evaluated and the formulation presented a good safety profile. ADV7103 provided an effective prolonged release of alkalising salts to cover a 12-h effect with adequate tolerability and could afford a twice a day (morning and evening) dosing in patients requiring long-term treatment.

Laser writing of nanostructured silicon arrays for the SERS detection of biomolecules with inhibited oxidation.

The present work reports the processing of laser irradiated Si arrays (LISi) and underlines their surface enhanced Raman scattering (SERS) functionality. A nanostructured Si/SiOx surface forms providing additional fluidic and photoprotective properties. Because of their optical and surface characteristics, the arrays exhibit a SERS analytical enhancing factor of 500, without any noble metals such as gold or silver. Micro-Raman maps allowed studying LISi properties, identifying maximum amplification in nanostructured areas characterized by the presence of 7 nm Si nanocrystals. These structures are confined by a SiOx layer as illustrated by XPS valence band measurements. The highly hydrophilic LISi areas allow a pre-concentration of target molecules prior to SERS analysis. A relevant application of LISi was found in the detection of apomorphine (APO), a drug used for the treatment of Parkinson's disease. In contrast with what is obtained by using gold SERS substrates, LISi allows the detection of APO with no sign of oxidation. This invites for the use of the Si/SiOx SERS detection in future systems for the personalized delivery of APO.

Surface micro- and nano-texturing of stainless steel by femtosecond laser for the control of cell migration.

The precise control over the interaction between cells and the surface of materials plays a crucial role in optimizing the integration of implanted biomaterials. In this regard, material surface with controlled topographic features at the micro- and nano-scales has been proved to affect the overall cell behavior and therefore the final osseointegration of implants. Within this context, femtosecond (fs) laser micro/nano machining technology was used in this work to modify the surface structure of stainless steel aiming at controlling cell adhesion and migration. The experimental results show that cells tend to attach and preferentially align to the laser-induced nanopatterns oriented in a specific direction. Accordingly, the laser-based fabrication method here described constitutes a simple, clean, and scalable technique which allows a precise control of the surface nano-patterning process and, subsequently, enables the control of cell adhesion, migration, and polarization. Moreover, since our surface-patterning approach does not involve any chemical treatments and is performed in a single step process, it could in principle be applied to most metallic materials.

Direct laser writing of nanorough cell microbarriers on anatase/Si and graphite/Si.

The formation of hierarchical structures consisting of microstripe barriers decorated with nanorough ablated materials prepared by direct laser writing is described. Linear features of circa 25µm width and 12µm height are achieved on amorphous and crystalline titania and graphitic carbon films deposited on silicon. Ablated protrusions build up barriers decorated by nanoscale Si-film reconstructions, as indicated by EDX maps and micro-Raman spectroscopy. Wettability tests show a dramatic change in water contact angle, which leads to almost full wetting after irradiation, irrespective of the original film composition. Fluorescence microscopy images of human mesenchymal stem cells cultured on 1D and 2D structures demonstrate the short term biocompatibility of the ablated surfaces. It is shown that cells adhere, extend and polarize on feature edges, independently of the type of surface, thus suggesting that the created nanoroughness is at the origin of the antifouling behavior. In particular, irradiated anatase and graphite surfaces demonstrate an increased performance of crystalline films for the creation of cell guiding and trapping devices. The results suggest that such laser processing of films may serve as a time-and-cost-efficient method for the design of few-cells analytical surfaces.

Luminescence and fine structure correlation in ZnO permeated porous silicon nanocomposites.

Nanocomposites formed by porous silicon (PS) and zinc oxide (ZnO) have potential for applications in optoelectronic devices. However, understanding the distribution of both materials in the nanocomposite, and especially the fine structure of the synthesized ZnO crystals, is key for future device fabrication. This study focuses on the advanced characterization of a range of PS-ZnO nanocomposites by using photon- and ion-based techniques, such as X-ray absorption spectroscopy (XAS) and elastic backscattering spectroscopy (EBS), respectively. PS substrates formed by the electrochemical etching of p(+)-type Si are used as host material for the sol-gel nucleation of ZnO nanoparticles. Different properties are induced by annealing in air at temperatures ranging from 200 °C to 800 °C. Results show that wurtzite ZnO nanoparticles form only at temperatures above 200 °C, coexisting with Si quantum dots (QDs) inside a PS matrix. Increasing the annealing temperature leads to structural and distribution changes that affect the electronic and local structure of the samples changing their luminescence. Temperatures around 800 °C activate the formation of a new zinc silicate phase and transform PS into an amorphous silicon oxide (SiOx, x≈ 2) matrix with a noticeably reduced presence of Si QDs. Thus, these changes affect dramatically the emission from these nanocomposites and their potential applications.

Porous silicon-cyclodextrin based polymer composites for drug delivery applications.

One of the main applications of porous silicon (PSi) in biomedicine is drug release, either as a single material or as a part of a composite. PSi composites are attractive candidates for drug delivery systems because they can display new chemical and physical characteristics, which are not exhibited by the individual constituents alone. Since cyclodextrin-based polymers have been proven efficient materials for drug delivery, in this work ß-cyclodextrin-citric acid in-situ polymerization was used to functionalize two kinds of PSi (nanoporous and macroporous). The synthesized composites were characterized by microscopy techniques (SEM and AFM), physicochemical methods (ATR-FTIR, XPS, water contact angle, TGA and TBO titration) and a preliminary biological assay was performed. Both systems were tested as drug delivery platforms with two different model drugs, namely, ciprofloxacin (an antibiotic) and prednisolone (an anti-inflammatory), in two different media: pure water and PBS solution. Results show that both kinds of PSi/ß-cyclodextrin-citric acid polymer composites, nano- and macro-, provide enhanced release control for drug delivery applications than non-functionalized PSi samples.

Calcium phosphate/porous silicon biocomposites prepared by cyclic deposition methods: spin coating vs electrochemical activation.

Porous silicon (PSi) provides an excellent platform for bioengineering applications due to its biocompatibility, biodegradability, and bioresorbability. However, to promote its application as bone engineering scaffold, deposition of calcium phosphate (CaP) ceramics in its hydroxyapatite (HAP) phase is in progress. In that sense, this work focuses on the synthesis of CaP/PSi composites by means of two different techniques for CaP deposition on PSi: Cyclic Spin Coating (CSC) and Cyclic Electrochemical Activation (CEA). Both techniques CSC and CEA consisted on alternate Ca and P deposition steps on PSi. Each technique produced specific morphologies and CaP phases using the same independent Ca and P stem-solutions at neutral pH and at room temperature. The brushite (BRU) phase was favored with the CSC technique and the hydroxyapatite (HAP) phase was better synthesized using the CEA technique. Analyses by elastic backscattering spectroscopy (EBS) on CaP/PSi structures synthesized by CEA supported that, by controlling the CEA parameters, an HAP coating with the required Ca/P atomic ratio of 1.67 can be promoted. Biocompatibility was evaluated by bone-derived progenitor cells, which grew onto CaP/PSi prepared by CSC technique with a long-shaped actin cytoskeleton. The density of adhered cells was higher on CaP/PSi prepared by CEA, where cells presented a normal morphological appearance and active mitosis. These results can be used for the design and optimization of CaP/PSi composites with enhanced biocompatibility for bone-tissue engineering.

Reprogramming hMSCs morphology with silicon/porous silicon geometric micro-patterns.

Geometric micro-patterned surfaces of silicon combined with porous silicon (Si/PSi) have been manufactured to study the behaviour of human Mesenchymal Stem Cells (hMSCs). These micro-patterns consist of regular silicon hexagons surrounded by spaced columns of silicon equilateral triangles separated by PSi. The results show that, at an early culture stage, the hMSCs resemble quiescent cells on the central hexagons with centered nuclei and actin/ß-catenin and a microtubules network denoting cell adhesion. After 2 days, hMSCs adapted their morphology and cytoskeleton proteins from cell-cell dominant interactions at the center of the hexagonal surface. This was followed by an intermediate zone with some external actin fibres/ß-catenin interactions and an outer zone where the dominant interactions are cell-silicon. Cells move into silicon columns to divide, migrate and communicate. Furthermore, results show that Runx2 and vitamin D receptors, both specific transcription factors for skeleton-derived cells, are expressed in cells grown on micropatterned silicon under all observed circumstances. On the other hand, non-phenotypic alterations are under cell growth and migration on Si/PSi substrates. The former consideration strongly supports the use of micro-patterned silicon surfaces to address pending questions about the mechanisms of human bone biogenesis/pathogenesis and the study of bone scaffolds.

Design and characterization of biofunctional magnetic porous silicon flakes.

Magnetic porous silicon flakes (MPSF) were obtained from mesoporous silicon layers formed by multi-step anodization and subsequent composite formation with Fe oxide nanoparticles by thermal annealing. The magnetic nanoparticles adhered to the surface and penetrated inside the pores. Their structure evolved as a result of the annealing treatments derived from X-ray diffraction and X-ray absorption analyses. Moreover, by tailoring the magnetic load, the dynamic and hydrodynamic properties of the particles were controlled, as observed by the pressure displayed against a sensor probe. Preliminary functionality experiments were performed using an eye model, seeking potential use of MPSF as reinforcement for restored detached retina. It was observed that optimal flake immobilization is obtained when the MPSF reach values of magnetic saturation >10(-4)Am(2)g(-1). Furthermore, the MPSF were demonstrated to be preliminarily biocompatible in vitro. Moreover, New Zealand rabbit in vivo models demonstrated their short-term histocompatibility and their magnetic functionality as retina pressure actuators.

Characterization and cytocompatibility of hybrid aminosilane-agarose hydrogel scaffolds.

Agarose hydrogels containing aminopropyl triethoxy silane (APTS) have been prepared and evaluated as scaffolds for adhesion and proliferation of human mesenchymal stem cells (hMSCs). The preparation of the hydrogels involved the conventional melting of agarose in water followed by addition of APTS as functional group carrier. The resulting hydrogel supports have been studied by Fourier transformed infrared spectroscopy in order to get an insight into the hybrid molecular structure. X-ray photoelectron spectroscopy has been used for the analysis of the surface chemical composition of the hydrogels. It is deduced from these data that the resulting hybrid structure presents two phases with a clear tendency toward APTS surface segregation. Moreover, the observation of the desiccated hydrogel surfaces by atomic force microscopy shows that the films acquire a filament-mesh structure for increasing APTS content, while the pure agarose supports exhibit a granular structure. As a result of such a structure, the hydrogel surfaces show a hydrophobic behavior, as determined by water contact angle measurements. The biocompatibility of such platforms is supported by adhesion-proliferation assays performed with hMSCs. It is concluded that although adhesion is lower on APTS rich scaffolds, the proliferation rate on these surfaces is higher so that total number of proliferating cells does not significantly depend on APTS content in the hydrogels.

Hybrid titania-aminosilane platforms evaluated with human mesenchymal stem cells.

The properties of hybrid aminopropyltriethoxysilane-tetraisopropylorthotitanate (APTS-TIPT) platforms prepared by a sol-gel route have been explored, and their biocompatibility was assayed after culture of human mesenchymal stem cells (hMSCs). The organic content of this material was observed to be preferably surface-oriented as indicated by microanalytical techniques. Furthermore, the surface showed characteristic amino-silane bands when explored by Raman spectroscopy as well as indications of silane and titanate condensation. Surface activity of the amino groups was probed by ultraviolet-visible spectroscopy imine derivatization and chemical force spectroscopy, showing a pH-dependent surface charge-induced potential. hMSCs cultured onto these surfaces showed relevant differences with respect to their behavior on gelatin-coated glass plates. Even if with a lower proliferative rate than controls, the cells develop long cytosolic prolongations in osteogenic differentiation medium, thus, supporting the idea of an APTS-TIPT stimulated process.

Micro-spot, UV and wetting patterning pathways for applications of biofunctional aminosilane-titanate coatings.

The micropatterning of functional films for biomedical applications is a key part of the process leading to a precise application. In the present work we present three different methodologies to micro-design biofunctional aminosilane-titanate coatings. The chemical functionality of the surface immobilized amino groups was initially tested by surface characterization techniques. X-ray photoelectron spectroscopy was used to analyze the films before and after derivatization with Trifluoromethylbenzaldehyde while atomic force microscopy was used to study the adsorption kinetics onto these hybrid films. The three micropatterning pathways were selected for three different kinds of applications: (1) 300 microm spots were satisfactorily used for oligonucleotide immobilization, (2) Masked regions protected from UV irradiation were intensively coated by colloidal gold nanoparticles creating a drastic contrast with respect to the UV exposed areas, and (3) radial micro stripes, used afterwards for culturing cells, were created onto Si substrates by wetting from modified precursor solutions. The results are a clear indication of the versatility of hybrid aminosilane-titanate coatings for biomedical applications requiring micropatterned biofunctional surfaces.

Surface analysis of plasma-patterned biofunctional hybrid titanate-aminosilane xerogel films.

The functionalization and patterning of biomedical materials with enhanced surface activity is a main objective for the development of high-specificity biosensors. The surfaces of sol-gel condensed aminopropyltriethoxysilane-tetraisopropyl orthotitanate hybrid materials have been studied in order to describe the mechanisms that allow the fixation of amino groups. X-ray photoelectron spectra obtained from these surfaces are compared with those coming from the surfaces of plasma-etched coatings. The results show that aminopropyl radicals remain on the surface after room-temperature condensation and that they are drastically removed after partial etching of the coating in an Ar plasma. This confirms that the functionalization is effectively a surface feature and suggests that amino groups may remain at the surface covalently bonded to the original amorphous Si-O- structure. Further evidence of the surface functionalization efficiency is illustrated with contact angle and zeta-potential measurements. It is complementarily proved by confocal microscopy that masked regions conserve their molecular activity and are not affected by the etching process. These facts suggest that these materials could play an active role when incorporated into biosensor devices.

Development of human mesenchymal stem cells on DC sputtered titanium nitride thin films.

The biocompatible properties of titanium nitride (TiN) have opened a new field of applications for this material. In the present work, TiN coatings with thicknesses around 1 microm have been prepared by DC magnetron sputtering. The aim has been to evaluate the adherence, growth and proliferation of human pluripotent mesenchymal stem cells (hMSCs) on the surface of TiN films with contrasted structural, electrical, and mechanical properties. For this purpose, the films were characterized by X-ray diffraction, scanning electron microscopy, sheet resistance measurements, and nanoindentation. Biological tests show that hMSCs adhere and proliferate onto TiN surfaces. The combination of the mechanical, electrical, and biological responses suggest that TiN coatings present appropriate properties to induce the in vitro stimulated differentiation of hMSCs. This possibility gives an added value to TiN based biomaterial coatings.