Synergistic integration of bio-mineralized nanoparticles and porous microsphere scaffolds for dual bioactive delivery in bone regeneration.

Conventional bone grafts face challenges in clinical applications, including donor shortages, immunological rejection, and mismatched degradation rates. This work introduces a porous microsphere scaffold loaded with self-assembled tea polyphenolic‑magnesium biomineralized nanoparticles to synergistically enhance antibacterial and osteogenic properties through a dual-factor spatiotemporal controlled release approach. Employing a biomimetic mineralization mechanism that mimics natural bone mineral formation, these nanoparticles integrate tea polyphenols with magnesium ions. This method achieves pH-responsive release kinetics: the antimicrobial component releases more effectively in mildly acidic infection microenvironments, while the mineral phase acts as a buffer against burst release, maintaining consistent local medication concentrations. Complementing this sustained-release behavior, polytrimethylene carbonate microspheres degrade via surface erosion, thereby extending therapeutic efficacy through dual "degradation-release" regulation. In vitro studies demonstrated effective eradication of methicillin-resistant Staphylococcus aureus biofilms, along with significant enhancement of osteoblast proliferation, differentiation, and mineralization activities by the scaffold. The scaffold's porous structure mimics cancellous bone, providing an appropriate compression modulus (∼195 MPa), supporting cell infiltration, and facilitating nutrient transport, thereby simulating the three-dimensional architecture of native bone tissue. Moreover, the scaffold modulates macrophage polarization toward the M2 phenotype and stimulates the secretion of anti-inflammatory cytokines (IL-37, IL-10), thereby fostering a favorable bone immune microenvironment. This work establishes a multifunctional bone tissue engineering platform by integrating spatiotemporal delivery (dual controlled release) with biomimetic mineral stabilization. By addressing infection control, promoting bone regeneration, and modulating immune responses simultaneously, this scaffold presents a promising solution for complicated infected bone defects.