In situ Engineered Silicon-Magnesium Implants Orchestrate Sequential Immunomodulation, Angiogenesis, and Osteogenesis for Bone Repair

Magnesium (Mg) is a promising candidate for next-generation bone implants due to its favorable mechanical properties and biodegradability. However, its rapid corrosion causes local alkalization, hydrogen release, and inflammation, severely limiting clinical translation. Herein, we developed a multifunctional Mg-based implant, denoted as Mg/Mg 2 SiO 4 /PDA (MSP), by constructing an in situ Mg 2 SiO 4 interlayer on the Mg substrate through a one-pot hydrothermal process, followed by polydopamine (PDA) functionalization. This multilayered design orchestrates sequential bone regeneration: early antiinfection-immunoregulation and late vascularization and osteogenesis, which main arises from the different degradation rate and time-window effects of the PDA and Mg-Si layers. By harnessing a controlled initial alkaline burst, the implant effectively inhibits bacterial infection, with bacterial survival rates all below 20%, while the subsequent PDA-mediated immunomodulation promotes macrophage polarization toward the pro-regenerative M2 phenotype and suppressing pro-inflammatory cytokines. Concurrently, controlled release of Si 4+ and Mg 2+ from the Mg 2 SiO 4 layer, synergized with PDA, enhances endothelial cell migration and angiogenesis. Sustained Mg 2+ release further supports osteogenesis, amplified by the synergistic effects of Si 4+ and PDA. MSP exhibited effective antioxidative capacity, potent antibacterial activity, and excellent cytocompatibility, with co-culture studies using rat adipose-derived stem cells (rADSCs) confirming robust osteoinduction. MSP significantly enhanced new bone formation and early-stage osseointegration, with BV/TV increased by 73% versus the Mg at 8 weeks. This innovative surface engineering strategy integrates immunoregulatory, pro-angiogenic, and osteoinductive functionalities, offering a transformative approach for Mg-based implants in bone regeneration within complex inflammatory microenvironments.