A Self‐Oxidizing <i>o</i>‐Dihydroxybenzene‐Based Covalent Organic Framework Hydrogel with Broad‐Spectrum Antibacterial Properties for Promoting Diabetic Wound Healing

Abstract Given the inherent limitations of current nano‐based antimicrobial materials, including their restricted broad‐spectrum efficacy and challenges in practical application, it is essential to develop an innovative therapeutic platform that effectively alleviates these shortcomings. Herein, inspired by the cryptic antimicrobial properties of natural marine mussels, an o ‐dihydroxybenzene‐based covalent organic framework (TAPT‐2,3DHA‐COF) is successfully synthesized, which exhibits potent broad‐spectrum antibacterial activity through the auto‐oxidative release of antibacterial agents. At the minimum inhibitory concentrations (MICs), potent antibacterial effects (&gt; 90% inhibition) are observed against six common and even resistant bacterial strains, including Staphylococcus aureus (1024 µg mL −1 ), Escherichia coli (512 µg mL −1 ), Pseudomonas aeruginosa (256 µg mL −1 ), methicillin‐resistant Staphylococcus aureus (MRSA; 1024 µg mL −1 ), etc. Encouraged by the aforementioned excellent performance, a hybrid acrylamide hydrogel covalent organic framework (Gel@COF) is constructed, which combines the advantages of both components, including robust antibacterial activity, mechanical stability, and biocompatibility. Notably, the potent healing‐promoting capability of Gel@COF is demonstrated in diabetic mice models with MRSA‐infected wounds, achieving an impressive wound healing rate of 99.62%. This work not only broadens the application of COFs in the field of antimicrobials but also provides a new strategy for developing advanced anti‐infective materials in the future.