BMP-2 releasing mineral-coated microparticle-integrated hydrogel system for enhanced bone regeneration

Introduction: Large bone defects (LBD) caused by trauma, infection, and tumor resection remain a significant clinical challenge. Although therapeutic agents such as bone morphogenetic protein-2 (BMP-2), have shown substantial potency in various clinical scenarios, their uncontrollable release kinetics has raised considerable concern from the clinical viewpoint. Mineral-coated microparticle (MCM) has shown its excellent biologics loading and delivery potential due to its superior protein-binding capacity and controllable degradation behaviors; thus, it is conceivable that MCM can be combined with hydrogel systems to enable optimized BMP-2 delivery for LBD healing. Methods: Herein, BMP-2 was immobilized on MCMs via electrostatic interaction between its side chains with the coating surface. Subsequently, MCM@BMP-2 is anchored into a hydrogel by the crosslinking of chitosan (CS) and polyethylene glycol (PEG). Results and Discussion: This microparticle–hydrogel system exhibits good biocompatibility, excellent vascularization, and the sustained release of BMP-2 in the bone defect. Furthermore, it is observed that this microsphere–hydrogel system accelerates bone formation by promoting the expression of osteogenesis-related proteins such as RUNX2, osteopontin, and osteocalcin in bone marrow mesenchymal stem cells (BMSCs). Thus, this newly developed multifunctional microparticle–hydrogel system with vascularization, osteogenesis, and sustained release of growth factor demonstrates an effective therapeutic strategy toward LBD.