A Microenvironment-Adaptive Hydrogel Enabled by an MXene-Based Coordination Nanoreactor Drives Immune-Osteogenic Cascade for Infected Bone Defects Regeneration
Infected bone defects remain a formidable clinical challenge due to the coupled pathologies of bacterial infection and impaired osteogenesis. Conventional treatments often fail to address the dynamic microenvironment, leading to persistent infection and inadequate bone repair. Here, we report a microenvironment-adaptive hydrogel incorporating a Ti3C2Tx MXene-based coordination nanoreactor that orchestrates an immune-osteogenic cascade. The nanoreactor, constructed by coordinating Fe3+ ions onto MXene nanosheets, exhibits pH- and reactive oxygen species (ROS)-responsive release of Fe3+ and MXene, enabling sequential antibacterial and pro-osteogenic activities. In vitro studies demonstrated that the hydrogel eradicated Staphylococcus aureus and Escherichia coli (>99.9% killing) within 6 h via synergistic photothermal and chemodynamic effects, while simultaneously scavenging excess ROS to mitigate oxidative stress. Notably, the released Fe3+ ions promoted M2 macrophage polarization, as evidenced by a 2.5-fold increase in CD206 expression, and subsequently enhanced osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs), with alkaline phosphatase activity elevated by 1.8-fold and alizarin red staining intensity increased by 2.2-fold. In a rat model of infected calvarial defects, the hydrogel significantly accelerated bone regeneration, achieving a bone volume fraction of 78.4% at 8 weeks post-implantation, compared to 35.2% in the untreated control. Micro-CT and histological analyses confirmed robust new bone formation and complete infection clearance. This study presents a paradigm for designing adaptive biomaterials that integrate infection control and bone regeneration, offering a promising strategy for treating infected bone defects.