Bioactive injectable composites based on insulin-functionalized silica particles reinforced polymeric hydrogels for potential applications in bone tissue engineering

Novel bioactive injectable composites based on biopolymeric hydrogels reinforced with insulin-functionalized silica particles were synthesized. The insulin (INS) was immobilized on the surface of amine-modified silica particles employing covalent attachment by EDC/NHS chemistry and via electrostatic interaction. The resulting formulations were examined for the morphology (SEM), chemical composition (FTIR, XPS) as well as protein content. To facilitate the injectability and support the bone regeneration, developed particles were dispersed in biopolymeric sol composed of collagen, chitosan and lysine-modified hyaluronic acid and crosslinked with genipin. By means of rheological study, the sol-gel in situ transition of obtained systems was verified. It was found in vitro study that MG-63 cells cultured on the developed composites exhibit significantly higher alkaline phosphatase (ALP) activity, compared to the pristine hydrogel. Furthermore, the biomineralization ability in the simulated body fluid (SBF) model was also demonstrated. Our findings suggest that proposed herein novel hydrogel-based composites might be the promising formulation for regeneration of bone defects, especially as a less-cost effective support/alternative for BMP-2 systems.