Multi-functional Bio-HJzyme: revolutionizing diabetic skin regeneration with its glucose-unlocked sterilization and programmed anti-inflammatory effects

Antibacterial dynamic therapy (ADT) triggered by reactive oxygen species (ROS) is promising for diabetic infectious disease treatment. However, the limited local O₂/H₂O₂ production and post-treatment inflammation remain long-standing issues. To address these challenges, a novel H₂-evolving bio-heterojunction enzyme (Bio-HJzyme) consisting of graphite-phase carbon nitride/copper sulfide (CN/Cu_2−xS) heterojunction and glucose oxidase (GOx) is created. The Bio-HJzyme offers glutathione peroxidase (GPx), peroxidase (POD), and catalase (CAT) mimetic activities; provides anti-pathogen properties via programmed light activation; and effectively promotes diabetic wound healing. Specifically, its GPx-mimetic activity and the presence of GOx significantly enhance the yield of H₂O₂, which can be catalyzed through POD-mimetic activity to produce highly germicidal •OH. The H₂O₂ can also be catalyzed to H₂O and O₂, assisted by the CAT-mimetic activity. The catalyzed products can then be catalyzed into germicidal •OH and •O₂⁻ under NIR light irradiation, giving enhanced ADT. Further, CN can split water to form H₂ 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.