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

Diabetic\nwounds are extremely difficult to heal due to their susceptibility\nto infections and a dysfunctional microenvironment, including high\nblood glucose, persistent inflammation, and excessive reactive oxygen\nspecies (ROS). Herein, we developed a multifunctional natural hydrogel\nwith a hypoglycemic effect and anti-inflammation, antioxidation, and\nantibacterial activities, by simple thermal-initiated ring-opening\npolymerization of natural B vitamin lipoic acid (LA) and natural polyphenol\ntannic acid (TA). Owing to the dynamicity of disulfide bonds, the\nresulting LA/TA(5) hydrogel could gradually degrade and release LA\nand TA. The released TA with good antibacterial activity could kill\napproximately 90% of bacteria to resist wound infection. Moreover,\nthe released LA and TA could normalize the dysfunctional microenvironment\nby downregulating blood sugar levels, eliminating ROS, and reducing\ninflammation to promote angiogenesis, thus accelerating diabetic wound\nrepair. The in vivo experiments showed that the healing rate of LA/TA(5)\nhydrogel-treated diabetic wounds was close to that of normal wounds.\nTherefore, the simple and multifunctional natural LA/TA(5) hydrogel\nwith the capacity to normalize the dysfunctional microenvironment\nholds great potential in clinical diabetic wound care.