Piezoelectric and Dielectric Electrospun Fluoropolymer Membranes for Oral Mucosa Regeneration: A Comparative Study.

Wound healing of the oral mucosa is an urgent problem in modern dental surgical practice. This research article presents and compares the findings of the investigations of the structural, physicochemical, and biological characteristics of two types of polymeric membranes used for the regeneration of oral mucosa. The membranes were prepared from poly(tetrafluoroethylene) (PTFE) and a copolymer of vinylidene fluoride and tetrafluoroethylene (VDF-TeFE) and analyzed via scanning electron microscopy, atomic force microscopy, X-ray diffraction analysis, and Fourier transform infrared spectroscopy. Investigation results obtained indicate that both types of membranes are composed of thin fibers: (0.57 ± 0.25) µm for PTFE membranes and (0.43 ± 0.14) µm for VDF-TeFE membranes. Moreover, the fibers of VDF-TeFE membranes exhibit distinct piezoelectric properties, which are confirmed by piezoresponse force microscopy and X-ray diffraction. Both types of membranes are hydrophobic: (139.7 ± 2.5)° for PTFE membranes and (133.5 ± 2.0)° for VDF-TeFE membranes. In vitro assays verify that both membrane types did not affect the growth and division of mice fibroblasts of the 3T3-L1 cell line, with a cell viability in the range of 88-101%. Finally, in vivo comparative experiments carried out using Wistar rats demonstrate that the piezoelectric VDF-TeFE membranes have a high ability to regenerate oral mucosa.

Antibacterial Calcium Phosphate Coatings for Biomedical Applications Fabricated via Micro-Arc Oxidation.

A promising method for improving the functional properties of calcium-phosphate coatings is the incorporation of various antibacterial additives into their structure. The microbial contamination of a superficial wound is inevitable, even if the rules of asepsis and antisepsis are optimally applied. One of the main problems is that bacteria often become resistant to antibiotics over time. However, this does not apply to certain elements, chemical compounds and drugs with antimicrobial properties. In this study, the fabrication and properties of zinc-containing calcium-phosphate coatings that were formed via micro-arc oxidation from three different electrolyte solutions are investigated. The first electrolyte is based on calcium oxide, the second on hydroxyapatite and the third on calcium acetate. By adding zinc oxide to the three electrolyte solutions, antibacterial properties of the coatings are achieved. Although the same amount of zinc oxide has been added to each electrolyte solution, the zinc concentration in the coatings obtained vary greatly. Furthermore, this study investigates the morphology, structure and chemical composition of the coatings. The antibacterial properties of the zinc-containing coatings were tested toward three strains of bacteria-Staphylococcus aureus, methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa. Coatings of calcium acetate and zinc oxide contained the highest amount of zinc and displayed the highest zinc release. Moreover, coatings containing hydroxyapatite and zinc oxide show the highest antibacterial activity toward Pseudomonas aeruginosa, and coatings containing calcium acetate and zinc oxide show the highest antibacterial activities toward Staphylococcus aureus and methicillin-resistant Staphylococcus aureus.

Electrospun Poly-L-Lactic Acid Scaffolds Surface-Modified via Reactive Magnetron Sputtering Using Different Mixing Ratios of Nitrogen and Xenon.

Controlled regeneration processes involving tissue growth using the surface and structure of scaffolds, are actively used in tissue engineering. Reactive magnetron sputtering is a versatile surface modification method of both metal and polymer substrates, as the properties of the formed coatings can be modified in a wide range by changing the process parameters. In magnetron sputtering, the working gas and its composition have an influence on the chemical composition and physical characteristics of the obtained coatings. However, there are no studies addressing the influence of the nitrogen/xenon gas mixture ratio in direct current magnetron sputtering on the deposition rate, physicochemical and in vitro properties of surface-modified biocompatible poly-L-lactic acid scaffolds. In this study, the application of mixtures of nitrogen and xenon in various ratios is demonstrated to modify the surface of non-woven poly-L-lactic acid scaffolds by direct current magnetron sputtering of a titanium target. It has been found that the magnetron sputtering parameters chosen do not negatively influence the morphology of the prepared scaffolds, but increase the hydrophilicity. Moreover, quantitative spectroscopic analysis results indicate that the formed coatings are primarily composed of titanium oxide and titanium oxynitride compounds and is dependent on the gas mixture ratio only to a certain extent. Atomic force microscopy investigations of the roughness of the fibers of the electrospun scaffolds and the thickness of the coatings formed on them show that the considerable variations observed in the intrinsic fiber reliefs are due to the formation of a fine layer on the fiber surfaces. The observed decrease in roughness after plasma modification is due to temperature and radiation effects of the plasma. In vitro experiments with human osteosarcoma cells show that the scaffolds investigated here have no cytotoxic effect on these cells. The cells adhere and proliferate well on each of the surface-modified electrospun scaffolds, with stimulation of cell differentiation in the osteogenic direction.

Improvement of the Surface Properties of Polyether Ether Ketone via Arc Evaporation for Biomedical Applications.

Polyether ether ketone is a bioinert polymer, that is of high interest in research and medicine as an alternative material for the replacement of bone implants made of metal. The biggest deficit of this polymer is its hydrophobic surface, which is rather unfavorable for cell adhesion and thus leads to slow osseointegration. In order to address this drawback, 3D-printed and polymer extruded polyether ether ketone disc samples that were surface-modified with titanium thin films of four different thicknesses via arc evaporation were investigated and compared with non-modified disc samples. Depending on the modification time, the thickness of the coatings ranged from 40 nm to 450 nm. The 3D-printing process does not affect the surface or bulk properties of polyether ether ketone. It turned out that the chemical composition of the coatings obtained did not depend on the type of substrate. Titanium coatings contain titanium oxide and have an amorphous structure. Microdroplets formed on the sample surfaces during treatment with an arc evaporator contain a rutile phase in their composition. Surface modification of the samples via arc evaporation resulted in an increase in the arithmetic mean roughness from 20 nm to 40 nm for the extruded samples and from 40 nm to 100 nm for the 3D-printed samples, with the mean height difference increasing from 100 nm to 250 nm and from 140 nm to 450 nm. Despite the fact that the hardness and reduced elastic modulus of the unmodified 3D-printed samples (0.33 GPa and 5.80 GPa) are higher than those of the unmodified extruded samples (0.22 GPa and 3.40 GPa), the surface properties of the samples after modification are approximately the same. The water contact angles of the polyether ether ketone sample surfaces decrease from 70° to 10° for the extruded samples and from 80° to 6° for the 3D-printed samples as the thickness of the titanium coating increases, making this type of coating promising for biomedical applications.

Antibacterial Activity and Cytocompatibility of Electrospun PLGA Scaffolds Surface-Modified by Pulsed DC Magnetron Co-Sputtering of Copper and Titanium.

Biocompatible poly(lactide-co-glycolide) scaffolds fabricated via electrospinning are having promising properties as implants for the regeneration of fast-growing tissues, which are able to degrade in the body. The hereby-presented research work investigates the surface modification of these scaffolds in order to improve antibacterial properties of this type of scaffolds, as it can increase their application possibilities in medicine. Therefore, the scaffolds were surface-modified by means of pulsed direct current magnetron co-sputtering of copper and titanium targets in an inert atmosphere of argon. In order to obtain different amounts of copper and titanium in the resulting coatings, three different surface-modified scaffold samples were produced by changing the magnetron sputtering process parameters. The success of the antibacterial properties' improvement was tested with the methicillin-resistant bacterium Staphylococcus aureus. In addition, the resulting cell toxicity of the surface modification by copper and titanium was examined using mouse embryonic and human gingival fibroblasts. As a result, the scaffold samples surface-modified with the highest copper to titanium ratio show the best antibacterial properties and no toxicity against mouse fibroblasts, but have a toxic effect to human gingival fibroblasts. The scaffold samples with the lowest copper to titanium ratio display no antibacterial effect and toxicity. The optimal poly(lactide-co-glycolide) scaffold sample is surface-modified with a medium ratio of copper and titanium that has antibacterial properties and is non-toxic to both cell cultures.

Surface Modification of Additively Fabricated Titanium-Based Implants by Means of Bioactive Micro-Arc Oxidation Coatings for Bone Replacement.

In this work, the micro-arc oxidation method is used to fabricate surface-modified complex-structured titanium implant coatings to improve biocompatibility. Depending on the utilized electrolyte solution and micro-arc oxidation process parameters, three different types of coatings (one of them-oxide, another two-calcium phosphates) were obtained, differing in their coating thickness, crystallite phase composition and, thus, with a significantly different biocompatibility. An analytical approach based on X-ray computed tomography utilizing software-aided coating recognition is employed in this work to reveal their structural uniformity. Electrochemical studies prove that the coatings exhibit varying levels of corrosion protection. In vitro and in vivo experiments of the three different micro-arc oxidation coatings prove high biocompatibility towards adult stem cells (investigation of cell adhesion, proliferation and osteogenic differentiation), as well as in vivo biocompatibility (including histological analysis). These results demonstrate superior biological properties compared to unmodified titanium surfaces. The ratio of calcium and phosphorus in coatings, as well as their phase composition, have a great influence on the biological response of the coatings.

Polyether Ether Ketone Coated with Ultra-Thin Films of Titanium Oxide and Zirconium Oxide Fabricated by DC Magnetron Sputtering for Biomedical Application.

Recently, polyether ether ketone has raised increasing interest in research and industry as an alternative material for bone implants. This polymer also has some shortcomings, as it is bioinert and its surface is relatively hydrophobic, causing poor cell adhesion and therefore slow integration with bone tissue. In order to improve biocompatibility, the surface of polyether ether ketone-based implants should be modified. Therefore, polished disc-shaped polyether ether ketone samples were surface-modified by direct current magnetron sputtering with ultrathin titanium and zirconium coatings (thickness < 100 nm). The investigation results show a uniform distribution of both types of coatings on the sample surfaces, where the coatings mostly consist of titanium dioxide and zirconium dioxide. Differential scanning calorimetry revealed that the crystalline structure of the polyether ether ketone substrates was not changed by the coating deposition. Both coatings are amorphous, as shown by X-ray diffraction investigations. The roughness of both coating types increases with increasing coating thickness, which is beneficial for cell colonization. The coatings presented and investigated in this study improve wettability, increasing surface energies, in particular the polar component of the surface energies, which, in turn, are important for cell adhesion.

Surface Modification of Electrospun Bioresorbable and Biostable Scaffolds by Pulsed DC Magnetron Sputtering of Titanium for Gingival Tissue Regeneration.

In this study, polymer scaffolds were fabricated from biodegradable poly(lactide-co-glycolide) (PLGA) and from non-biodegradable vinylidene fluoride-tetrafluoroethylene (VDF-TeFE) by electrospinning. These polymer scaffolds were subsequently surface-modified by sputtering titanium targets in an argon atmosphere. Direct current pulsed magnetron sputtering was applied to prevent a significant influence of discharge plasma on the morphology and mechanical properties of the nonwoven polymer scaffolds. The scaffolds with initially hydrophobic properties show higher hydrophilicity and absorbing properties after surface modification with titanium. The surface modification by titanium significantly increases the cell adhesion of both the biodegradable and the non-biodegradable scaffolds. Immunocytochemistry investigations of human gingival fibroblast cells on the surface-modified scaffolds indicate that a PLGA scaffold exhibits higher cell adhesion than a VDF-TeFE scaffold.

Biodegradable magnesium fuel-based Janus micromotors with surfactant induced motion direction reversal.

The speed and motion directionality of bubble-propelled micromotors is dependent on bubble lifetime, bubble formation frequency and bubble stabilization. Absence and presence of bubble stabilizing agents should significantly influence speed and propulsion pattern of a micromotor, especially for fast-diffusing molecules like hydrogen. This study demonstrates a fully biodegradable Janus structured micromotor, propelled by hydrogen bubbles generated by the chemical reaction between hydrochloric acid and magnesium. Six different concentrations of hydrochloric acid and five different concentrations of the surfactant Triton X-100 were tested, which also cover the critical micelle concentration at a pH corresponding to an empty stomach. The Janus micromotor reverses its propulsion direction depending on the availability and concentration of a surfactant. Upon surfactant-free condition, the Janus micromotor is propelled by bubble cavitation, causing the micromotor to be pulled at high speed for short time intervals into the direction of the imploding bubble and thus backwards. In case of available surfactant above the critical micelle concentration, the Janus micromotor is pushed forward by the generated bubbles, which emerge at high frequency and form a bubble trail. The finding of the propulsion direction reversal effect demonstrates the importance to investigate the motion properties of artificial micromotors in a variety of different environments prior to application, especially with surfactants, since biological media often contain large amounts of surface-active components.

Nitrogen-doped titanium dioxide films fabricated via magnetron sputtering for vascular stent biocompatibility improvement.

Nowadays, vascular stents are commonly used to treat cardiovascular diseases. This article focuses on the influence of nitrogen doping of titanium dioxide thin films, utilized for coating metallic stents to improve their biological properties and biocompatibility. The hereby-investigated titanium oxide thin films are fabricated by magnetron sputtering in a reactive gas atmosphere consisting of argon and oxygen in the first case and argon, nitrogen and oxygen in the second case. Control of the nitrogen and oxygen gas flow rates, and hence their mixing ratios, allows adjustment of the nitrogen-doping level within the titanium dioxide thin films. A correlation of the thin film internal structure on the in vitro behavior of human mesenchymal stem cells derived from adipose tissue is hereby demonstrated. Different nitrogen doping levels affect the surface energy, the wettability, the cell adhesion and thus the cellular proliferation on top of the thin films. The surface colonization of cells on titanium dioxide thin films decreases up to a nitrogen-doping level of âˆ¼ 3.75 at.%, which is associated with a decreasing polar component of the surface energy. For non-doped titanium dioxide thin films, a weak chondrogenesis of adult human adipose-derived mesenchymal stem cells with lower chondrogenic differentiation compared to glass is observed. An increasing nitrogen-doping level leads to linear increase in the chondrogenic differentiation rate, which is comparable to the control value of uncoated glass. Other investigated differentiated cell types do not display this behavior.

Alginate Microparticle Arrays as Self-Polishing Bio-Fouling Release Coatings.

Biofouling is a severe problem of any water borne structure. Since the ban of tin-organic compounds and expected bans of other poisonous chemical formulations in the near future, replacement of these compounds are sought. This study investigates antibiofouling properties of micro- and nanostructured alginate layer films. Alginate is a natural product from brown algae and was in this study electro-sprayed and crosslinked with divalent calcium and copper ions to produce homogeneous micro- and nanoparticles. These calcium- and copper-alginate particles were assembled into micro- and nanostructured layer films and the antifouling properties of these low elastic modulus, hydrophilic, biodegradable system were evaluated with the microalgae chlorella. Comparison with pristine glass slides, smooth copper- and calcium alginate bulk films was performed. The comparison shows less biofouling for smooth bulk films compared to micro-nanostructured alginate, while all alginate systems are less bio-fouled on long timescales compared to pristine glass.

Magnetically-guided hydrogel capsule motors produced via ultrasound assisted hydrodynamic electrospray ionization jetting.

Hydrogel capsules are a potential candidate for drug delivery and an interesting alternative to polyelectrolyte multilayer capsules which are under investigation since 20 years. Recently introduced polyelectrolyte complex capsules produced by spraying are non-biodegradable and not biocompatible, which limits their practical application, while biodegradable alginate capsules require complex coaxial electrospray ionization jetting. In this work, biodegradable alginate capsules cross-linked by calcium are successfully produced by hydrodynamic electrospray ionization jetting with the assistance of low frequency ultrasound. The size and shape of most capsules show significant differences with respect to different spraying distance, spraying mode, electrode shape and spraying concentration. Capsules in the shape of vase, mushrooms and spheres were successfully produced. Average capsule size can be adjusted from 10 µm to 2 mm. These capsules are used to encapsulate a model drug. Encapsulated paramagnetic particles enable defined directional motion under the propulsion of a rotating magnetic field, while model drugs can be released by ultrasound.

Magnetically-propelled hydrogel particle motors produced by ultrasound assisted hydrodynamic electrospray ionization jetting.

One of the most promising future applications of hydrogels is drug delivery. The hydrogels act as a biomedical cargo model to reach the target and release drugs to cure diseases. This application requires no side effects of the hydrogel and the ability to pass through porous media (e.g. membranes, interstitial tissue etc.) with nanoscaled channels. At the same time, the hydrogel must be mass-producible in an economic way. In this work, we show that hydrodynamic electrospray ionization jetting combined with ultrasound can fulfill these high requirements. This method can produce mucoadhesive micro-/nano-particles, which are small enough to pass through the gastrointestinal epithelium. The average size of the produced particles is exactly predictable by controlling the spraying distance, spraying mode, alginate concentration, ultrasound bath frequency and counter electrode shape. These micro-/nano-particles are loaded with biocompatible magnetite nanoparticles, and propelled by a rotating magnetic field between 5 to 20 m T and a frequency from 1 Hz to 100 Hz. These rotating micro-/nano-particle motors perform directional motion in solution, offering a promising possibility for magnetically controlled drug delivery.

Hydrodynamic electrospray ionization jetting of calcium alginate particles: effect of spray-mode, spraying distance and concentration.

Hydrodynamic electrospray ionization jetting was applied for generating and characterizing calcium cross-linked alginate microparticles. These microparticles show different diameters and aspect ratios for three electrospray modes (dripping, conejet and multijet modes), four spraying distances (5, 10, 15 and 20 cm), and six spraying concentrations. Comparing the three different electrospray modes, we found that the conejet mode results in the smallest particle diameters, lowest aspect ratio and smallest variations over the parameter space mentioned above. For all spraying modes, the resultant particle diameters become independent of the spraying distance at a sprayed solute concentration ≥ 2.5%. The aspect ratio of microparticles varies significantly for different spraying modes and distances. An increasing aspect ratio of all spray modes was determined for sodium alginate spraying concentrations ≤ 1.5% and spraying distances of 20 cm; this phenomenon can be explained with the chain ejection effect. This systematic investigation offers a basic database for industrial applications of hydrodynamic electrospray ionization.