Thermosensitive Hydrogel Integrated with Bimetallic Nano‐Enzymes for Modulating the Microenvironment in Diabetic Wound Beds

Abstract Effective regulation and reconstruction of the microenvironment are critical for the regeneration of chronic wounds. Diabetic wounds, in particular, pose a significant clinical challenge due to increased oxidative stress and dysfunctional healing processes. In this study, a novel therapeutic strategy is developed using 3D copper‐magnesium bimetallic antioxidant nano‐enzymes (Cu/Mg‐MOF) to mitigate reactive oxygen species (ROS) and restore redox balance through electron transfer. To optimize delivery, a thermo‐sensitive hydrogel composed of chitosan (CS) and ε ‐polylysine (PL) is designed, serving as an efficient carrier for the nano‐enzymes. This Cu/Mg‐MOF@CS/PL hydrogel exhibits excellent physical properties, including injectability, softness, and biocompatibility, making it ideal for application in diabetic wounds. In a diabetic wound model, treatment with Cu/Mg‐MOF@CS/PL hydrogel significantly accelerated wound healing, with a closure rate of 90.6% by day 14, compared to just 55.4% in the untreated group. The hydrogel effectively promoted key aspects of wound healing, such as collagen deposition, re‐epithelialization, angiogenesis, and immunomodulation. These findings underscore the potential of the Cu/Mg‐MOF@CS/PL hydrogel as a promising therapeutic system for enhancing the healing of diabetic wounds.