Polyphenol‐Regulated Bimetallic Artificial Metalloproteinases with Broad‐Spectrum RONS Scavenging Activities for Diabetic Wound Repair

Abstract Although numerous enzyme‐mimicking nanomaterials have been developed to regulate the highly reactive oxygen species (ROS)‐rich microenvironment of diabetic wounds for improving its healing, the poor broad‐spectrum ROS‐scavenging capacity and biological toxicity resulting from side reactions of nanomaterials still require improvement. To tackle these challenges, a polyphenol‐mediated copper‐bismuth bimetallic artificial metalloproteinases, CuBi‐TA@BSA, based on a protein‐scaffold design strategy, is conceptually engineered. The Bi and polyphenols can cooperatively enhance the loading capacity of Cu ions and regulate their coordination microenvironment within the BSA scaffold. The CuBi‐TA@BSA exhibits remarkable scavenging activity against various ROS via effectively donating electrons, as well as the reaction pathway specificity of catalytic H₂O₂ decomposition without POD‐like activity. Moreover, in vitro and in vivo studies further confirm that the CuBi‐TA@BSA can protect cells from oxidative damage, inhibit the onset and progression of inflammation, and promote diabetic wound healing. This work presents a simple strategy for biocatalysts to effectively scavenge ROS and accelerate the diabetic wound‐healing process, also provides a strategy for designing artificial metalloproteinases for antioxidative therapy.