Controlled drug delivery from chitosan-coated heparin-loaded nanopores anodically grown on nitinol shape-memory alloy.

Nitinol (NiTi shape-memory alloy) is an interesting candidate in various medical applications like dental, orthopedic, and cardiovascular devices, owing to its unique mechanical behaviors and proper biocompatibility. The aim of this work is the local controlled delivery of a cardiovascular drug, heparin, loaded onto nitinol treated by electrochemical anodizing and chitosan coating. In this regard, the structure, wettability, drug release kinetics, and cell cytocompatibility of the specimens were analyzed in vitro. The two-stage anodizing process successfully developed a regular nanoporous layer of Ni-Ti-O on nitinol, which considerably decreased the sessile water contact angle and induced hydrophilicity. The application of the chitosan coatings controlled the release of heparin mainly by a diffusional mechanism, where the drug release mechanisms were evaluated by the Higuchi, first-order, zero-order, and Korsmeyer-Pepass models. Human umbilical cord endothelial cells (HUVECs) viability assay also showed the non-cytotoxicity of the samples, so that the best performance was found for the chitosan-coated samples. It is concluded that the designed drug delivery systems are promising for cardiovascular, particularly stent applications.

Drug-delivery Ca-Mg silicate scaffolds encapsulated in PLGA.

The aim of this work is to develop dual-functional scaffolds for bone tissue regeneration and local antibiotic delivery applications. In this respect, bioresorbable bredigite (Ca7MgSi4O16) porous scaffolds were fabricated by a foam replica method, loaded with vancomycin hydrochloride and encapsulated in poly lactic-co-glycolic acid (PLGA) coatings. Field emission scanning electron microscopy, Archimedes porosimetry and Fourier-transform infrared spectroscopy were used to characterize the structure of the scaffolds. The drug delivery kinetics and cytocompatibility of the prepared scaffolds were also studied in vitro. The bare sample exhibited a burst release of vancomycin and low biocompatibility with respect to dental pulp stem cells based on the MTT assay due to the fast bioresorption of bredigite. While keeping the desirable characteristics of pores for tissue engineering, the biodegradable PLGA coatings modified the drug release kinetics, buffered physiological pH and hence improved the cell viability of the vancomycin-loaded scaffolds considerably.

PLGA-coated drug-loaded nanotubes anodically grown on nitinol.

This study evaluates the use of nanotubes (NTs) as a matrix for local drug delivery modified by a biodegradable polymeric coating on medical-grade nitinol (NiTi alloy) surfaces. For this purpose, NiTi was anodized within parameters that promote the formation of NTs, ultrasonicated, annealed and impregnated with vancomycin hydrochloride. To improve bioperformance, poly(lactic-co-glycolic acid) (PLGA) was also deposited on the drug-loaded NTs. The samples were characterized in terms of structure, wettability, drug delivery, corrosion and cytocompatibility. Scanning electron microscopy and water contact angle measurements signify the formation of open-top homogeneous NTs of 600- 700 nm in length and ~30 nm in diameter with improved hydrophilicity. The bare antibiotic-impregnated NTs exhibit a burst release of about 49% of the loaded drug in the first 6 h of soaking in a physiological medium, followed by the entire drug diffusing out before 96 h. The PLGA coating effectively controls the burst release of vancomycin to 26% and retains almost 50% of the loaded drug beyond 7 days. The kinetics of the different vancomycin-release stages is also correlated to several well-established models. As a comparative criterion of metallic ions leaching kinetics, the corrosion resistance of nitinol is found to be reduced by the formation of the NTs, while the PLGA coating enhances this electrochemical feature. Due to the alteration of the drug delivery and corrosion protection, the PLGA-coated vancomycin-impregnated sample presents a higher dental pulp stem cell viability in comparison to both the bare drug-loaded and non-loaded NTs. In conclusion, PLGA-coated vancomycin-loaded NT-covered NiTi can be effectively used as a controlled drug-delivery device, while having a drug-release dosage within the therapeutic window and a minimal negative effect on biocompatibility.

Co-incorporation of strontium and fluorine into diopside scaffolds: Bioactivity, biodegradation and cytocompatibility evaluations.

This study focuses on the effect of Sr-, F-, and their co-doping on the structure, biodegradation, bioactivity and cytocompatibility of diopside-based scaffolds, using X-ray diffraction, Raman spectroscopy, field-emission scanning electron microscopy, Archimedes densitometry, inductively coupled plasma spectroscopy, pH-metry, and cell MTT assay. The structural characterization of the scaffolds confirmed the successful incorporation of the dopants into the ceramic. In addition, all the doped scaffolds presented higher apatite-forming ability levels in comparison to the undoped one, where the highest and the least impact of doping on bioactivity belonged to F- and co-doping, respectively. It was found that the biodegradation difference of the scaffolds in terms of principal ions and the chance of F-incorporation into precipitated apatite determine the bioactivity difference of the samples. Osteoblast-like MG-63 cells exhibited the highest and lowest compatibility to the Sr-doped and co-doped scaffolds, respectively. In summary, F- and Sr-doping offered the highest bioactivity and cytocompatibility, respectively, whereas co-doping presented the weakest behaviors comparatively.

Surface modification of Ti-6Al-4V alloy for osseointegration by alkaline treatment and chitosan-matrix glass-reinforced nanocomposite coating.

Individual and combined treatments of alkaline (NaOH) and chitosan/bioactive glass (SiO2-CaO-MgO) nanocomposite coating were applied on Ti-6Al-4V alloy surfaces with the objective of investigating and improving i) wettability, ii) apatite-formation ability, iii) corrosion resistance, and iv) biocompatibility. Individual applications of each surface treatment were found to enhance hydrophilicity, apatite-forming ability, corrosion resistance, and cytocompatibility (MG-63 cells). The most improved properties, except apatite-formation ability, were obtained using the combined treatment yielding a reduction of 64 and 93% in sessile contact angle and corrosion rate, respectively, than the untreated substrate. These improvements originate from the desired roughness and apatite-formation ability of the alkaline treatment and the appropriate biocompatibility and corrosion protection of the nanocomposite coating. That is, the combined application of alkaline treatment and chitosan nanocomposite coating is demonstrated as a promising surface-engineering strategy for hard-tissue replacement applications.

Bioperformance of chitosan/fluoride-doped diopside nanocomposite coatings deposited on medical stainless steel.

This work focuses on the structure, bioactivity, corrosion, and biocompatibility characteristics of chitosan-matrix composites reinforced with various amounts of fluoride-doped diopside nanoparticles (at 20, 40, 60, and 80 wt%) deposited on stainless steel 316 L. Bioactivity studies reveal that the presence of the nanoparticles in the coatings induces apatite-forming ability to the surfaces. Based on electrochemical impedance spectroscopy and polarization experiments, the in vitro corrosion resistance of the substrate was enhanced by increasing the level of the nanoparticles in the coating. The sample containing 60% of the nanoparticles presented the highest osteoblast-like MG63 cell viability, in comparison to the other prepared and even control samples. Also, the cell attachment on the surfaces was improved with increasing the amount of the nanoparticles in the coatings. It is eventually concluded that the application of chitosan/fluoride-doped diopside nanocomposite coatings improves the bioperformance of metallic implants.

Is cell viability always directly related to corrosion resistance of stainless steels?

It has been frequently reported that cell viability on stainless steels is improved by increasing their corrosion resistance. The question that arises is whether human cell viability is always directly related to corrosion resistance in these biostable alloys. In this work, the microstructure and in vitro corrosion behavior of a new class of medical-grade stainless steels were correlated with adult human mesenchymal stem cell viability. The samples were produced by a powder metallurgy route, consisting of mechanical alloying and liquid-phase sintering with a sintering aid of a eutectic Mn-Si alloy at 1050 °C for 30 and 60 min, leading to nanostructures. In accordance with transmission electron microscopic studies, the additive particles for the sintering time of 30 min were not completely melted. Electrochemical impedance spectroscopic experiments suggested the higher corrosion resistance for the sample sintered for 60 min; however, a better cell viability on the surface of the less corrosion-resistant sample was unexpectedly found. This behavior is explained by considering the higher ion release rate of the Mn-Si additive material, as preferred sites to corrosion attack based on scanning electron microscopic observations, which is advantageous to the cells in vitro. In conclusion, cell viability is not always directly related to corrosion resistance in stainless steels. Typically, the introduction of biodegradable and biocompatible phases to biostable alloys, which are conventionally anticipated to be corrosion-resistant, can be advantageous to human cell responses similar to biodegradable metals.

Surface modification of stainless steel orthopedic implants by sol-gel ZrTiO4 and ZrTiO4-PMMA coatings.

In this paper, the biocompatibility of a medical-grade stainless steel coated with sol-gel derived, nanostructured inorganic ZrTiO4 and hybrid ZrTiO4-PMMA thin films is correlated with surface characteristics. The surfaces of the samples are characterized by atomic force microscopy, the sessile drop technique, and electrochemical corrosion experiments. The viability of adult human mesenchymal stem cells on the surfaces after one day of culture is also assessed quantitatively and morphologically. According to the results, both of the coatings improve the hydrophilicity, corrosion resistance, and thereby cytocompatibility of the substrate. Despite the higher corrosion protection by the hybrid coating, the sample coated with the inorganic thin film exhibits a better cell response, suggesting the domination of wettability. In summary, the ZrTiO4-based sol-gel films can be considered to improve the biocompatibility of metallic implants.