Lipoic Acid-Based Multifunctional Hydrogel Modulates Aberrant Microenvironments to Promote Diabetic Wound Healing

Diabetic wounds are difficult to heal because of persistent infection and a dysregulated microenvironment characterized by hyperglycemia, prolonged inflammation, and excessive production of reactive oxygen species. Herein, we develop a multifunctional natural hydrogel with antibacterial, antioxidant, and immunoregulatory properties through the thermally initiated ring-opening polymerization of α-lipoic acid. The incorporation of chlorogenic acid and allicin enhanced the structural stability of the hydrogel, while enabling sustained release of chlorogenic acid during degradation. The hydrogel effectively reduced oxidative stress, promoted angiogenesis, and modulated the inflammatory response, thereby improving the local wound microenvironment and facilitating tissue repair. In a diabetic wound model, the hydrogel significantly accelerated wound closure and promoted tissue regeneration compared with a commercial wound dressing. These findings demonstrate that the multifunctional α-lipoic acid-based hydrogel provides a simple and effective strategy to regulate the dysfunctional microenvironment of diabetic wounds and shows considerable potential for diabetic wound management.