pH-triggered in situ mineralized NIR-II nanozyme hydrogel enables spatiotemporally controlled antibacterial therapy and microenvironment reprogramming for infected bone defect repair.

Abstract

Infected bone defects remain a significant clinical challenge due to bacterial colonization-induced persistent inflammation, oxidative stress, and local acidification, which collectively impair bone regeneration. Conventional approaches, including antibiotic therapy and bone grafting, are often insufficient to concurrently eradicate infection and promote tissue repair. Herein, we report a multifunctional GelMA-Au@Pt@CaP (GAPCP) hydrogel that integrates second near-infrared window (NIR-II, 1000-1700 nm) photothermal antibacterial activity, nanozyme-mediated antioxidant catalysis, and programmable Ca2+/PO₄3- release to enable synergistic antibacterial and osteogenic therapy. Upon 1064 nm laser irradiation, the Au@Pt nanozyme achieves efficient bacterial ablation and biofilm disruption via photothermal effects. The calcium phosphate (CaP) layer provides responsive ion delivery to enhance osteogenic differentiation and mineralization. Concurrently, the porous Pt shell catalyzes H₂O₂ decomposition under acidic conditions, mitigating oxidative stress and hypoxia. GAPCP scavenges intracellular reactive oxygen species, promotes macrophage polarization toward an anti-inflammatory M2 phenotype, and enhances angiogenic and osteogenic activities in vitro. In an infected calvarial defect model, GAPCP combined with NIR-II irradiation achieves simultaneous antibacterial, anti-inflammatory and bone regenerative outcomes. Transcriptomic analysis reveals that these effects are associated with the coordinated regulation of inflammatory signaling, ion transport, and angiogenesis pathways. This work establishes a NIR-II-responsive multifunctional hydrogel platform that couples infection eradication with microenvironment remodeling to drive bone regeneration, providing a promising strategy for treating infected bone defects.