Calcium-Specific-Binding PLGA Microspheres with Embedded BMP-2 for Bone Regeneration

Bone morphogenetic protein-2 (BMP-2) is a potent osteoinductive factor for bone regeneration, but its rapid clearance and dose-dependent adverse effects limit its clinical use. This study developed calcium-binding poly(butyl methacrylate-co-methacryloyloxyethyl phosphate) (PBMP)-coated poly(lactide-co-glycolide) (PLGA) microparticles to enhance calcium-rich surface anchoring and enable sustained BMP-2 release. Microparticles were characterized for morphology, zeta potential, encapsulation efficiency, release kinetics, and hydroxyapatite (HA)-binding affinity, and were further evaluated for in vivo efficacy. PBMP coating markedly increased the HA-binding affinity of PLGA microparticles. Encapsulation efficiency was over 55%, and BMP-2 was released in a sustained manner over 30 days, with the cumulative release gradually approaching a plateau during the later incubation period. When applied to a rat calvarial defect model, the PBMP-coated microparticle (BMP-2-PLGA/PBMP) group showed the greatest bone volume fraction, bone surface area, and trabecular number, along with the lowest trabecular separation compared to the free BMP-2 and control groups. Histological analysis confirmed denser and more mature bone matrix formation in the BMP-2-PLGA/PBMP group. These findings demonstrate that PBMP-coated PLGA microparticles provide HA-targeted, sustained BMP-2 delivery, resulting in improved bone regeneration and microarchitecture. This delivery platform represents a promising strategy for more effective bone defect repair.