A Self‐Adaptive CoNi‐Based Metal–Organic Framework for Autonomous Antibacterial Efficacy and Anti‐Inflammatory Resolution in Accelerated Wound Healing

Delayed healing of bacterially infected wounds stems from drug-resistant bacterial invasion and excessive reactive oxygen species (ROS)-driven inflammation, which necessitating strategies that simultaneously eradicate pathogens and resolve inflammation. We designed a bimetallic CoNi-based metal-organic framework (CoNi-MOF) with enhanced multienzyme-like activities: oxidase-like (OXD-like), peroxidase-like (POD-like), and catalase-like (CAT-like) activities. The superior performance arises from the synergy between Co and Ni, which shifts the d-band center of Co closer to the Fermi level than those in Co-MOF and Ni-MOF. This electronic structure enhancement facilitates substrate adsorption and lowers reaction energy barriers, accounting for the strong enzyme-like activities of CoNi-MOF. At acidic infection sites, OXD-like and POD-like activities are activated to generate antibacterial ROS, effectively eliminating drug-resistant bacteria. As bacterial clearance occurs and the wound returns to neutrality, CoNi-MOF exhibits CAT-like activity and radical scavenging capabilities to eliminate excess ROS, thereby restoring oxidative balance and mitigating inflammation. Moreover, CoNi-MOF promotes macrophage polarization from the pro-inflammatory M1 phenotype toward the pro-regenerative M2 phenotype. This pH-responsive enzymatic activity offers a self-adaptive therapeutic strategy, as validated by in vivo studies showing accelerated wound healing. This self-adaptive nanozyme platform integrates antibacterial, antioxidant, and immunomodulatory functions, offering a promising antibiotic-free treatment for drug-resistant bacterial wound infections.