Co-assembling of natural drug-food homologous molecule into composite hydrogel for accelerating diabetic wound healing

Diabetic wound healing is a major clinical challenge due to its vulnerability to bacterial infection and the prolonged inflammation in the wound. Traditional dressings for the healing of diabetic wounds are often suffered from unsatisfactory efficacy and frequent dressing changes which may cause secondary damage. Therefore, it is necessary to find a wound dressing that balances material functionality, degradation, safety, and tissue regeneration. Our recent studies demonstrated that gallic acid (GA) could spontaneously form supramolecular hydrogels at a relatively high concentration. However, a single network of GA hydrogel is prone to degradation, poor adhesion, and poor swelling, and may not be suitable for wound healing dressings. In this study, a composite hydrogel (GAK) was constructed by introducing konjac glucomannan (KGM) into the gel system of gallic acid (GA) and applied to promote diabetic wound healing. The composite hydrogel (GAK) with superior surface adhesion, stability, and swelling properties than the single-network of GA hydrogel. Moreover, in vitro experiments showed that GAK hydrogel had excellent biocompatibility and exhibited antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). Additionally, the GAK hydrogel could significantly accelerate angiogenesis, collagen deposition, and re-epithelialization during wound healing in diabetic mice, reducing the expression of related inflammatory proteins interleukin-1β (IL-1β), tumor necrosis factor-alpha (TNF-α), and cyclooxygenase-2 (COX-2), and improving the wound closure rate. The findings of this study suggest that this composite hydrogel (GAK) can be an ideal dressing material for accelerating diabetic wound healing.