A Multifunctional and Self‐Adaptive Hydrogel with on‐Demand Bactericidal/Anti‐Inflammatory for Synergistic Multi‐Enzyme‐H 2 Therapy and Monitoring of Diabetic Wounds

ABSTRACT Chronic diabetic wounds exhibit delayed healing due to hyperglycemia, bacterial infection, and oxidative stress. To overcome this limitation, a multifunctional composite hydrogel (APBT‐AuPt/C 3 N 4 ) is constructed by integrating AuPt‐modified g‐C 3 N 4 nanosheets (AuPt/C 3 N 4 ) with a pH‐responsive boronic acid probe. The Schottky junction‐enhanced charge separation endows AuPt/C 3 N 4 with improved multi‐enzyme‐like activities (glucose oxidase‐like, oxidase‐like, and peroxidase‐like) and efficient photocatalytic hydrogen production. Therefore, AuPt/C 3 N 4 not only consumes glucose and generates reactive oxygen species (ROS) to kill bacteria, but also reduces inflammation via photocatalytic H 2 generation, dynamically balancing the bactericidal/anti‐inflammatory process. The pH‐responsive hydrogel system built with the boron‐tannin (BT) probe allows real‐time monitoring of wound status and guides light‐controlled and on‐demand anti‐inflammatory therapy. In vitro experiments demonstrate that APBT‐AuPt/C 3 N 4 hydrogel exhibits highly efficient bactericidal activity against both Gram‐positive and Gram‐negative bacteria, including Staphylococcus aureus ( S. aureus ) and Escherichia coli ( E. coli ). In diabetic mouse models, treatment with APBT‐AuPt/C 3 N 4 combined with light irradiation significantly accelerated wound closure, promoted collagen deposition and angiogenesis, and downregulated the expression of pro‐inflammatory cytokines (IL‐1β, IL‐6, TNF‐α). This study presents a non‐invasive, tunable nanozyme‐H 2 synergistic therapy, offering a promising strategy for diabetic wound management.