Multi‐Functional Bio‐HJzyme: Revolutionizing Diabetic Skin Regeneration with its Glucose‐Unlocked Sterilization and Programmed Anti‐Inflammatory Effects

Abstract Antibacterial dynamic therapy (ADT) triggered by reactive oxygen species (ROS) is promising for diabetic infectious disease treatment. However, the limited local O 2 /H 2 O 2 production and post‐treatment inflammation remain long‐standing issues. To address these challenges, a novel H 2 ‐evolving bio‐heterojunction enzyme (Bio‐HJzyme) consisting of graphite‐phase carbon nitride/copper sulfide (CN/Cu 2− x S) heterojunction and glucose oxidase (GO x ) is created. The Bio‐HJzyme offers glutathione peroxidase (GP x ), peroxidase (POD), and catalase (CAT) mimetic activities; provides anti‐pathogen properties via programmed light activation; and effectively promotes diabetic wound healing. Specifically, its GP x ‐mimetic activity and the presence of GO x significantly enhance the yield of H 2 O 2 , which can be catalyzed through POD‐mimetic activity to produce highly germicidal •OH. The H 2 O 2 can also be catalyzed to H 2 O and O 2 , assisted by the CAT‐mimetic activity. The catalyzed products can then be catalyzed into germicidal •OH and •O 2 − under NIR light irradiation, giving enhanced ADT. Further, CN can split water to form H 2 under solar light, which dramatically suppresses the inflammation caused by excessive ROS. In vivo evaluation confirms that Bio‐HJzyme promotes the regeneration of diabetic infectious skin through killing bacteria, enhancing angiogenesis, promoting wound bed epithelialization, and reinforcing anti‐inflammatory responses; hence, providing a revolutionary approach for diabetic wounds healing.