Diabetic Microenvironment‐Unlocked BioHJzyme with H₂S Evolution for Robust Anti‐Pathogens and Hyperinflammatory Wound Regeneration Through TGF‐β/Smad Pathway

Abstract Deferred diabetic skin healing is an ever‐growing complication owing to the hyperglycemic microenvironment, which accelerates the generation of advanced glycated end products (AGEs) and provides a hotbed for pathogenic infection. Here, the H 2 S‐evolving bio‐heterojunction enzyme (BioHJzyme), which is consisted by MXene/FeS 2 and glucose oxidase (GOx) is devised. It presents glutathione peroxidase (GPx)‐ and peroxidase (POD)‐mimetic antibacterial activity for anti‐pathogens and wound regeneration by AGEs depression. The GOx catalyzes glucose, resulting in reducing the bacterial nutrient and supplying H 2 O 2 . The POD‐mimetic activity of the BioHJzyme catalyzes the H 2 O 2 to hydroxyl radical (•OH) with a turnover number of 4.45 × 10 −1 s −1 , while the GPx‐mimetic activity of it consumes glutathione for further •OH accumulation. The anti‐pathogens can be enhanced by near infrared laser (NIR) irradiation owing to the efficient separation of electron‐hole pairs originated from the heterostructure, which presents NIR‐activatable •OH and 1 O 2 production. Moreover, the BioHJzyme evolves H 2 S in acidic environment, acting as an H 2 S donor, which protects cells around the wound from oxidative damage and AGEs, rescues mitochondrial respiration, improves the extracellular matrix deposition and ameliorates dysfunction of fibroblasts for diabetic skin regeneration through TGF‐β/Smad pathway. The work provides a proof‐of‐concept for bacteria‐invaded diabetic wound regeneration via H 2 S‐evolving BioHJzyme.