A dual-pronged glycopeptide hydrogel promotes diabetic wound healing by synchronizing metabolic-angiogenic recoupling

Chronic diabetic wounds pose a significant clinical challenge due to their complex pathophysiology and limited treatment options. In this study, we developed a dual-pronged glycopeptide hydrogel (OPAD-M) based on oxidized glucomannan (OGM) and poly (γ-glutamic acid) grafted with hydrazide and dopamine groups (PAD), incorporating bioactive Mg²⁺ ions. The OPAD-M hydrogel exhibits excellent porosity, self-healing, and adhesive properties owing to the dynamic covalent Schiff base bonds and metal-coordination interactions within its crosslinked network. In vitro, the screened OPAD-M hydrogel inhibited pro-inflammatory factors expression, promoted cell migration and angiogenesis via PI3K/AKT pathways. Furthermore, the new mechanism revealed that the OPAD-M hydrogel accelerated angiogenesis by upregulating the expression of glycolysis-related genes, resulting in collagen deposition and rapid wound closure in diabetic wound mice. Collectively, these findings underscore the potential of the OPAD-M hydrogel as a promising strategy for metabolic modulation and effective diabetic wound healing in diverse clinical applications.