Carboxymethyl Chitosan‐Based Antioxidant Hydrogel Accelerates Diabetic Wound Healing

Abstract Diabetic wound healing is hampered due to oxidative stress, exacerbated inflammation, and impaired angiogenesis in the wounds. A pH‐sensitive antioxidant hydrogel based on carboxymethyl chitosan (CMCS), oligoprocyanidins (OPC), and oxide dextran (Oxd) is prepared to accelerate diabetic wound healing. The hydrogel network is formed via imine and hydrogen bonding interactions in the presence of hydroxyl, amino, and aldehyde groups, and deferoxamine (DFO) is incorporated into the hydrogel. The hydrogel shows pH‐triggered drug release, a good antioxidant, and anti‐inflammatory properties, and can promote tube formation and cell migration in vitro. Moreover, the hydrogel can accelerate wound healing in streptozotocin (STZ)‐induced diabetic mice by regulating the inflammation environment with up‐regulation of anti‐inflammatory factors (IL‐4 and IL‐10) and down‐regulation of pro‐inflammatory factors (TNF‐α and IL‐6), and promoting angiogenesis with up‐regulation of HIF‐1α, VEGF, and CD31. Thus, the pH‐sensitive antioxidant hydrogel provides a promising therapeutic strategy for diabetic wound healing.