Glucose-Triggered Cascade ROS-Regulating via Metal-Hybrid Hydrogen-Bonded Organic Framework Integrated Hydrogels for Diabetic Wound Healing.

Abstract

Chronic diabetic wounds are difficult to heal due to sustained hyperglycemia, excessive oxidative stress, bacterial biofilm infection, and impaired immune regulation. Current wound dressings often lack the ability to sense pathological glucose levels and to deliver antibacterial and regenerative functions in a controlled and coordinated manner. Here, we develop a glucose-responsive catalytic hydrogel that integrates enzyme-metal hybrid nanozymes within a dynamic polymer network for intelligent diabetic wound therapy. Glucose oxidase (GOx) is immobilized in a hydrogen-bonded organic framework (HOF) to form stable nanozymes, while Cu2+ ions are incorporated to enable glucose-triggered cascade catalysis, initiating a Fenton-like reaction for localized antibacterial action. These nanozymes are embedded into a self-healing hydrogel based on oxidized sodium alginate (OSA), carboxymethyl chitosan (CMCS), and acrylamide (Am), forming a tough and bio-adhesive scaffold through dynamic Schiff-base cross-linking. The resulting hydrogel exhibits glucose-regulated reactive oxygen species generation, efficient biofilm eradication, redox-mediated immune modulation, and enhanced angiogenesis, thereby accelerating diabetic wound healing both in vitro and in vivo. This work presents a biocompatible and spatially organized enzyme-metal-hydrogel platform that couples metabolic sensing with controlled chemodynamic therapy, offering a promising strategy for next-generation intelligent wound dressings.