Zinc-induced photocrosslinked konjac glucomannan/glycyrrhizic acid hydrogel promotes skin wound healing in diabetic mice through immune regulation

Abstract

Diabetic wound healing is a complex process. Owing to the lack of effective wound dressings, diabetic wound healing is often delayed. Here, injectable composite hydrogels with methacrylic anhydride (MA)-modified Konjac glucomannan and Zn2+-induced glycyrrhizic acid self-assembly were developed for skin wound healing in diabetic mice. Under induction with a photoinitiator and Zn2+, the hydrogel formed rapidly (<5 s) in vitro. The KGMMA/GA/Zn hydrogel demonstrated excellent mechanical properties (strain [40 %] >28 KPa) and physicochemical characteristics, which enabled the adaptation to various complex skin wound environments. Crucially, in vitro and in vivo experiments revealed that the hydrogel had good biocompatibility and low hemolytic properties (1.7 %) and promoted cell migration and tube formation. Hydrogels can modulate the innate properties of the immune system, regulate the polarization of macrophages in the M2 direction, and inhibit the production of ROS and inflammatory factors without the addition of cytokines or drugs in vivo and in vitro. In vivo animal experiments revealed that the hydrogel significantly accelerated the repair process of skin wounds, with a repair efficiency reaching 97.2 %. In summary, this novel hydrogel constitutes a highly effective wound healing dressing and may be a promising approach in tissue regeneration engineering.