Polydopamine-Functionalized HMS/PLGA Composite Microsphere Scaffold Modulates Enhances Immunomodulation and Bone Repair.

The development of poly(lactic-co-glycolic acid) (PLGA)-based microsphere scaffolds with comprehensive osteogenic activity, hydrophilicity, mechanical strength, and biocompatibility remains a significant challenge. Here, we constructed a hexagonal mesoporous silica (HMS)/PLGA composite microsphere scaffold (HP). Subsequently, we further developed a polydopamine (PDA)-modified version of HP (PHP) by applying a PDA coating to its surface. Compared with HP, PHP exhibited improved compressive strength and hydrophilicity while maintaining desirable porosity. In vitro, PHP promoted BMSCs proliferation and osteogenic differentiation, upregulated osteogenic gene expression, and induced macrophage polarization toward the M2 anti-inflammatory phenotype. In a rat calvarial defect model, PHP significantly enhanced bone regeneration, as confirmed by micro-CT and histological analyses, and maintained elevated expression of BMP-2 and VEGF to support osteogenesis and angiogenesis. Immunostaining further demonstrated increased CD163 and decreased iNOS expression, indicating an immunomodulatory effect. All materials showed favorable biocompatibility. This work integrated the surface functionalization of PDA with the structural features of HMS, demonstrating that the ternary composite scaffold achieved simultaneous regulation of the immune microenvironment and osteogenesis, providing a promising strategy for clinically translatable bone repair materials.