Nano-SiO2 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 2 ) to produce nano-SiO 2 reinforced Alg–chitosan–gelatin nanocomposite hydrogels (Alg/SiO 2 –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 2 on the morphological structure, mechanical properties, thermal stability , rheological properties, swelling, biodegradability , biomineralization and cytocompatibility of the resultant Alg/SiO 2 -CHI-GA NCH. The experimental findings demonstrate that the constructed Alg/SiO 2 -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 2 –CHI–GA NCH were regulated to some extent by nano-SiO 2 content. Notably, nano-SiO 2 inclusion enhanced the attachment and viability of MG63 and MC3T3-E1 cells and induced three-dimensional cell growth in ALG/SiO 2 –CHI–GA NCH. Among the fabricated NCH, Alg/SiO 2 –CHI–GA NCH with 0.5% and 1.0% (w/v) nano-SiO 2 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 2 amount, indicating the favorable effect of nano-SiO 2 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.