Matrix vesicle-inspired delivery system based on nanofibrous chitosan microspheres for enhanced bone regeneration

Inspired by the initial mineralization process with bone matrix vesicles (MVs), this study innovatively developed a delivery system to mediate mineralization during bone regeneration. The system comprises nanofibrous chitosan microspheres (NCM) and poly (allylamine hydrochloride)-stabilized amorphous calcium phosphate (PAH-ACP), which is thereafter referred to as NCMP. NCM is synthesized through the thermal induction of chitosan molecular chains, serving as the carrier, while PAH-ACP functions as the mineralization precursor. Additionally, the nanofibrous network of NCMP mimics the architecture of natural extracellular matrix (ECM), creating an optimal niche for the active adhesion of stem cells to its surface, exhibiting good biocompatibility, immunoregulation, and osteogenic performance. In vivo, NCMP effectively recruits cells and mineralizes collagen, modulates cell behavior and differentiation, and promotes in situ biomineralization in rat calvarial defects. These results underscore the dual efficacy of NCMP not only as an effective delivery system for mineralization precursors but also as ECM-mimicking bio-blocks, offering a promising avenue for enhancing the repair and regeneration of bone defects.