Peptide Loaded Self-Healing Hydrogel promotes diabetic skin wound healing through macrophage orchestration and inflammation inhibition

Chronic wound is one of the complications of diabetes, and its difficult cure results in increased disability rate and mortality rate, which brings serious psychological and economic burden to patients. Excessive inflammation is one of the key reasons for poor tissue healing in chronic diabetic wounds. Herewith, the development of wound dressings with anti-inflammation and promoting tissue repair is of great significance for the treatment of chronic diabetic wounds. In this work, the Ac2-26 (Ac) peptide was loaded into the hyaluronic acid (HA) complex hydrogel for diabetic wound therapy. The hydrogel containing Ac had good mechanical properties, self-healing properties, and adhesion. It could down-regulate the M1/M2 phenotype of macrophages effectively, thereby promoting collagen type Ⅲ (COL-Ⅲ) secretion and migration of L929 and angiogenesis of HUVECs. Furthermore, the hydrogel containing Ac could restore the oxidative phosphorylation process and down-regulated toll-like receptor signaling pathway and inflammatory gene expression in the pathological environment of diabetes, showing a superior anti-inflammatory effect to ultimately promote the collagen deposition and angiogenesis in tissues for wounds repair. The HA complex hydrogel containing Ac demonstrated a good potential for clinical application in diabetic wound repair.