A upper critical solution temperature- and synergistic antioxidant-responsive tremella polysaccharide hydrogel for...

The high-sugar environment caused persistent inflammation at diabetic wound sites, resulting in impaired healing. Hydrogel dressings proved effective in addressing these issues. However, many still demonstrated insufficient wet adhesion, flexibility, or painless removability. These shortcomings often led to bleeding during dressing changes and resulted in further injury. To overcome these limitations, we developed an upper critical solution temperature (UCST) hydrogel. This material exhibited excellent mechanical properties and synergistic antioxidant effects, promoting the healing of diabetic wounds. This hydrogel was fabricated from a copolymer network of gelatin, sorbitol, and tremella polysaccharide (TP), with the addition of ergothioneine (EGT) and dipotassium glycyrrhizate (DPG) (ED@SG-T0.8). The abundant hydrogen bonds within the system improved the hydrogel's stability and tensile strength. This contributed to its outstanding mechanical properties and tight adhesion to skin. The hydrogel's straw-like structure facilitates efficient water and substance exchange, while its sol-gel transition at 43 °C (within skin tolerance range) prevents secondary injury during dressing changes. Notably, this study demonstrates synergistic antioxidant interactions between EGT and DPG, and between DPG and SG-T0.8, thereby effectively modulating the inflammatory micro-environment. In a type I diabetic mouse model, it accelerated wound healing by upregulating CD31 (promoting microvascular formation) and modulating cytokines (increased IL-10, decreased TNF-α), leading to significant MMP-9 downregulation. This study demonstrated that the ED@SG-T0.8 had a great potential in the treatment of diabetic wounds.