Nano-SiO reinforced alginate-chitosan-gelatin nanocomposite hydrogels with improved physicochemical properties and biological activity.

Alginate (Alg) hydrogels possess desirable advantages for application in tissue engineering; however, they are limited by their weak mechanical properties, poor chronical stability in phosphate buffered saline, and absence of mammalian cell recognition sites, severely restricting their biomedical applications. To overcome these limitations, we integrated Alg hydrogels with nano-silica (SiO) to produce nano-SiO reinforced Alg-chitosan-gelatin nanocomposite hydrogels (Alg/SiO-CHI-GA NCH) for biomedical purposes, utilizing Chitosan (CHI) and gelatin (GA) in an alternate electrostatic adsorption. Specifically, we investigated the regulatory and promotional effects of the nano-SiO on the morphological structure, mechanical properties, thermal stability, rheological properties, swelling, biodegradability, biomineralization and cytocompatibility of the resultant Alg/SiO-CHI-GA NCH. The experimental findings demonstrate that the constructed Alg/SiO-CHI-GA NCH exhibited uniform morphology and a regular structure. Upon freeze-drying, the internal cross-sections of the NCH exhibited a honeycomb porous structure. Furthermore, the physicochemical properties and biological activities of the prepared Alg/SiO-CHI-GA NCH were regulated to some extent by nano-SiO content. Notably, nano-SiO inclusion enhanced the attachment and viability of MG63 and MC3T3-E1 cells and induced three-dimensional cell growth in ALG/SiO-CHI-GA NCH. Among the fabricated NCH, Alg/SiO-CHI-GA NCH with 0.5% and 1.0% (w/v) nano-SiO exhibited significant proliferative activity, which is attributable to their high porosity and uniform cell adhesion. Furthermore, the alkaline phosphatase activity in the cells gradually increased with increasing of nano-SiO amount, indicating the favorable effect of nano-SiO on the osteogenic differentiation of MG63 and MC3T3-E1 cells. Our study findings provide a comprehensive foundation for the structural- and property-related limitations of Alg hydrogels in biomedicine, thereby expanding their potential applications in tissue engineering.