Synthesis, optimization, and cell response investigations of natural-based, thermoresponsive, injectable hydrogel: An attitude for 3D hepatocyte encapsulation and cell therapy.

For the purpose of developing a 3D vehicle for the delivery of hepatocytes in cell therapy, the improved system of crosslinker and new gelling agent combinations consisting of glycerophosphate and sodium hydrogen carbonate have been employed to produce injectable, thermoresponsive hydrogels based on chitosan and silk fibroin. Adjusting the polymer-to-gelling agent ratio and utilizing a chemical crosslinker developed hydrogel scaffolds with optimal gelling time and pH. Applying sodium hydrogen carbonate neutralizes chitosan while keeping its thermoresponsive characteristics and decreases glycerophosphate from 60% to 30%. Genipin boosts the mechanical properties of hydrogel without affecting the gel time. Due to their stable microstructure and lower amine availability, genipin-containing materials have a low swelling ratio, around six compared to eight for those without genipin. Hydrogels that are crosslinked degrade about half as fast as those that are not. The slowerr degradation of Silk fibroin compared to chitosan makes it an efficient degradation inhibitor in silk-containing formulations. All of the optimized samples showed less than 5% hemolytic activity, indicating that they lacked hemolytic characteristics. The acceptable cell viability in crosslinked hydrogels ranges from 72% to 91% due to the decreasing total salt concentration, which protects cells from hyperosmolality. The pH of hydrogels and their interstitial pores kept most encapsulated cells alive and functioning for 24 h. Urea levels are higher in the encapsulation condition compared to HepG2 cultivated alone, and this may be due to cell-matrix interactions that boost liver-specific activity. Urea synthesis in genipin crosslinked hydrogels increased dramatically from day 1 (about 4 mg dl-1) to day 3 (approximately 6 mg dl-1), suggesting the enormous potential of these hydrogels for cell milieu preparation. All mentioned findings represent that the optimized system may be a promising candidate for liver regeneration.

Effect of titanium dioxide intermediate layer on scratch and corrosion resistance of sol-gel-derived HA coating applied on Ti-6Al-4V substrate.

Modification of dental and orthopedic implants' surface by coating them with bioactive materials, such as hydroxyapatite (HA), diminishes the implants' fixation time. Appropriate adhesion to the substrate and stability in biological conditions are essential requirements for these coatings. In this study, sol-gel-derived HA coating was applied on the Ti-6Al-4 V substrate, which is a high-performance alloy for manufacturing bone implants. Also, titanium dioxide (TiO2) which was prepared by the sol-gel method was used as an intermediate layer between HA coating and the substrate. The nano-scratch and potentiodynamic polarization tests were employed to evaluate the effectiveness of TiO2 intermediate layer on improving the scratch resistance, as an indicator of coating adhesion strength, and the corrosion resistance of the coated samples. The quality of the coating bonded to the substrate was studied by cross-sectional SEM images. The XRD tests indicated that HA and TiO2 coatings were formed with predetermined phase compositions. The biocompatibility of sol-gel-derived HA coating was established by simulated body fluid (SBF) immersion tests. The SEM images, along with the results of electrochemical and nano-scratch tests, proved the significant effect of a TiO2 intermediate layer on improving the scratch resistance and stability of HA coating on titanium alloy substrate.

Effect of Dioxane and N-Methyl-2-pyrrolidone as a Solvent on Biocompatibility and Degradation Performance of PLGA/nHA Scaffolds

Background: Solvent casting/particulate leaching is one of the most conventional methods for fabricating polymer/ceramic composite scaffolds. In this method, the solvent generally affects resulting scaffold properties, including porosity and degradation rate. Methods: Herein, composite scaffolds of PLGA (poly(lactide-co-glycolide))/ nano-hydroxyapatite (nHA) with different percentages of nHA (25, 35, and 45 wt. %) were prepared by the solvent casting/particle leaching combined with freeze drying. The effects of two different solvents, 1,4-dioxane (DIO) and N-methyl-2-pyrrolidone (NMP), on morphology, porosity, bioactivity, degradation rate, and biocompatibility of the resulting scaffolds were investigated. Results: The results revealed that increasing the nano-hydroxyapatite (nHA) percentages had no significant effect on the porosity and interconectivity of scaffolds (p > 0.05), whereas altering the solvent from DIO into NMP decreased the porosity from about 87% into 71%, respectively. Moreover, scaffolds of DIO illustrated the high results of cell proliferation compared to those of NMP; the cell viability of GD25 decreased from 85% to 65% for GN25. The findings also indicated that scaffolds prepared by NMP had a higher rate of losing weight in comparison to DIO. Adding nHA to PLGA had a significant effect on the bioactivity of scaffolds (p < 0.05), composite scaffolds with 45 wt % nHA had at least 30% more weight gain compared to the neat polymer scaffolds. Conclusion: The DIO scaffolds have higher rates of porosity, interconnectivity, bioactivity, and biocompatibility than NMP scaffolds due to its high evaporation rate.

pH-Sensitive magnetite mesoporous silica nanocomposites for controlled drug delivery and hyperthermia.

In clinical applications, chemotherapy and hyperthermia are commonly used together. To achieve this, we synthesized multifunctional magnetite mesoporous silica nanoparticles (MMSNs) coated with a chitosan hydrogel. pH-Responsive chitosan hydrogels (cross-linked glutaraldehyde) were used to cover mesoporous silica pores. The infrared spectroscopy (FT-IR) and electron microscopy images (SEM and TEM) confirm that a hydrogel layer and a silica shell were formed. By applying alternating magnetic fields (AMF) to nanogels, heat generation (43 °C) occurred within a short time. The drug release (tamoxifen) of nanogels was studied for 72 h at different pH and temperatures. Drug release at pH 7.4/T = 37 °C (simulating physiological condition) and pH 5/T = 43 °C (pH simulating endosomes/hyperthermia) were 15 and 70%, respectively, so, drug release was increased with hyperthermia. To determine the biocompatibility of the nanogels, an MTT assay of L929 cells was performed for 24, 48 and 72 h. The results show high biocompatibility of nanogels even at high concentrations (over 80% cell viability after 72 h for all concentrations).

Evaluation of setting time and compressive strength of a new bone cement precursor powder containing Mg-Na-Ca.

Taking the advantage of a novel magnesium phosphate precursor containing Na and Ca, the cementation rate of the cement, including only Mg/Mg-Na-Ca, was studied. Besides, two effective parameters, that is, calcination temperature, 650 °C and 800 °C, and powder-to-cement liquid ratio, 1 and 1.5 g/mL, were assessed. X-ray diffraction, scanning electron microscopy, ion chromatography, particle size analyser, Vicat needle and compression test were used to characterize the powders and obtained cements. The sample containing Mg-Na-Ca, calcined at 800 °C with powder-to-cement liquid ratio of 1.5, obtained the highest compressive strength, 20 MPa, but set fast. To control the kinetics of cementation, the powder containing Mg-Na-Ca calcined at 950 °C with powder-to-cement liquid ratio of 1.5 and 2 g/mL was assessed and the one with 2 g/mL set in 9 min possessing 22 MPa compressive strength was selected as optimal condition to be used as a candidate, injectable bone cement.

Fabrication and characterization of poly(D,L-lactide-co-glycolide)/hydroxyapatite nanocomposite scaffolds for bone tissue regeneration.

Conventional methods in fabrication of scaffolds based on polymer/bioceramic composites frequently make use of solution casting then particle leaching. The residues of common organic solvents can get trapped in this technique hence provide safety concerns on final scaffold. In this study, N-methyl pyrrolidone was used as an approved solvent for parenteral pharmaceutical products especially implants with acceptable toxicological profile. A combined freeze drying and solvent casting methods were adopted for complete removal of the solvent from final scaffold structure. Biodegradable scaffolds based on poly (D,L-lactide-co-glycolide) and different percentages of nanohydroxyapatite (25, 35, and, 45% w/w) were characterized thoroughly regarding porosity, pore distribution as well as their bioactivity and biocompatibility. The results showed 70-80% porosity with a size distribution in the range of 50-200 mum for different conditions. Bioactivity of the scaffolds was directly dependent on the bioceramic content in the samples according to the results. Composites and neat samples showed the same cytocompatibility profile. (c) 2010 Wiley Periodicals, Inc. J Biomed Mater Res, 2010.

Biological evaluation of partially stabilized zirconia added HA/HDPE composites with osteoblast and fibroblast cell lines.

In the present study, the biocompatibility of partially stabilized zirconia (PSZ) added hydroxyapatite (HA)--high density polyethylene (HDPE) composites was evaluated by proliferation and cell attachment assays on two osteoblast cell lines (G-292, Saos-2) and a type of fibroblast cell isolated from bone tissue namely HBF in different time intervals. Cell-material interactions on the surface of the composites were observed by scanning electron microscopy (SEM). The effect of composites on the behavior of osteoblast and fibroblast cells was compared with those of HDPE and Tissue Culture Poly Styrene (TPS) (as negative control) samples. Results showed that the composite samples supported a higher proliferation rate of osteoblast cells in the presence of composite samples as compared to the HDPE and TPS samples after 3, 7 and 14 days of incubation period. It was showed that an equal or in some cases an even higher proliferation rate of G-292 and Saos-2 osteoblast cells on composite samples in compare to negative controls in culture period (P < 0.05). The number of adhered cells on the composite samples was equal and in some cases higher than the number adhered on the HDPE and TPS samples after the above mentioned incubation periods (P < 0.05). Adhered cells presented a normal morphology by SEM and many of the cells were seen to be undergoing cell division.