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.