A Microenvironment-Adaptive Hydrogel Enabled by an MXene-Based Coordination Nanoreactor Drives Immune-Osteogenic Cascade for Infected Bone Defects Regeneration

• • The MXene-based coordination nanoreactor hydrogel achieved >99.9% antibacterial efficacy against S. aureus and E. coli within 6 h, addressing the critical need for rapid infection control in bone defect management. • • The hydrogel promoted M2 macrophage polarization with a 2.5-fold increase in CD206 expression, demonstrating a shift from pro-inflammatory to pro-regenerative immune phenotype, which is essential for tissue repair. • • Osteogenic differentiation of BMSCs was enhanced, with alkaline phosphatase activity increased by 1.8-fold and alizarin red staining intensity by 2.2-fold, indicating robust osteoinductive properties. • • In vivo, the hydrogel achieved a bone volume fraction of 78.4% at 8 weeks in infected calvarial defects, compared to 35.2% in controls, representing a 2.2-fold improvement in bone regeneration, which is clinically significant for large bone defect repair.