Multifunctional Natural Hydrogel Enables Normalization of the Dysfunctional Microenvironment for Diabetic Wound Repair

Diabetic wounds are extremely difficult to heal due to their susceptibility to infections and a dysfunctional microenvironment, including high blood glucose, persistent inflammation, and excessive reactive oxygen species (ROS). Herein, we developed a multifunctional natural hydrogel with a hypoglycemic effect and anti-inflammation, antioxidation, and antibacterial activities, by simple thermal-initiated ring-opening polymerization of natural B vitamin lipoic acid (LA) and natural polyphenol tannic acid (TA). Owing to the dynamicity of disulfide bonds, the resulting LA/TA(5) hydrogel could gradually degrade and release LA and TA. The released TA with good antibacterial activity could kill approximately 90% of bacteria to resist wound infection. Moreover, the released LA and TA could normalize the dysfunctional microenvironment by downregulating blood sugar levels, eliminating ROS, and reducing inflammation to promote angiogenesis, thus accelerating diabetic wound repair. The in vivo experiments showed that the healing rate of LA/TA(5) hydrogel-treated diabetic wounds was close to that of normal wounds. Therefore, the simple and multifunctional natural LA/TA(5) hydrogel with the capacity to normalize the dysfunctional microenvironment holds great potential in clinical diabetic wound care.