Organic-inorganic hybrid carbonate apatite capsules combining environment-responsive drug release and osteogenic induction for bone regeneration

Bone defect repair requires biomaterials that simultaneously regenerate bone tissue and deliver localized drug therapy. In this study, we developed drug-loadable organic-inorganic hybrid capsules consisting of a carbonate apatite (CO₃Ap) shell and a thermoresponsive coacervate core. The capsules have a distinct core-shell structure, with coacervate droplets present in the core and the shell formed from CO₃Ap. This structure enables selective drug loading, sequestering hydrophobic low molecules in the core while efficiently adsorbing bone morphogenetic proteins, such as bone morphogenetic protein-2 (BMP-2), to the shell. Release studies revealed microenvironment-responsive behavior, characterized by rapid release of small molecules under acidic conditions mimicking bone remodeling and sustained release of BMP-2 at physiological pH. In vitro studies using MC3T3-E1 preosteoblast cells confirmed excellent cytocompatibility. Furthermore, CO₃Ap capsules significantly promoted osteogenic differentiation by increasing the expression of alkaline phosphatase, osteopontin, and osteocalcin. In vivo implantation into rat mandibular defects further promoted bone regeneration, with significant increases in bone mass and osteocalcin expression compared with control groups filled with free BMP-2 or capsules alone. These findings establish CO₃Ap capsules as a bone-regenerating biomaterial that combines low molecule and protein delivery with osteoinductive capabilities. This dual-functional platform offers a versatile and clinically relevant strategy for bone defect repair and serves as the foundation for next-generation therapeutic biomaterials.