Photothermal antibacterial antioxidant conductive self-healing hydrogel with nitric oxide release accelerates diabetic wound healing

Diabetic wound healing is affected by insufficient angiogenesis, oxidative damage, and bacterial infection, resulting in a delayed healing process. There is an urgent need to design a novel multifunctional wound dressing for promoting diabetic wound healing. Nitric oxide (NO) represents a promising wound healing agent because of its positive role in angiogenesis. Here, a series of antibacterial antioxidant self-healing conductive multifunctional hydrogels integrating near-infrared (NIR) laser irradiation NO release behavior, were developed based on carboxymethyl chitosan (CMCS), 2,3,4-trihydroxybenzaldehyde (THB), copper chloride (CuCl₂), and graphene oxide (GO)-N, N′-di-sec-butyl-N, N′-dinitroso-1,4-phenylenediamine (BNN6) (GO-BNN6, abbreviated as GB), to promote wound healing in Type I diabetes (TID). CMCS/THB/Cu/GB hydrogels show stable mechanical properties, self-healing ability, conductivity, antioxidant properties, intrinsic antibacterial properties, biocompatibility, etc. The addition of GB enabled the hydrogel to exhibit photothermal properties and photothermal-induced antibacterial activity in vitro. More importantly, the CMCS/THB/Cu/GB2 (2 mg/mL of GB in the hydrogel) was able to release NO under NIR laser irradiation. In a full-thickness skin wound model in diabetic mice, CMCS/THB/Cu/GB2 hydrogel combined with NIR laser treatment (CMCS/THB/Cu/GB2+NIR) can significantly accelerate wound contraction, collagen content, and angiogenesis. In conclusion, these multifunctional photothermal conductive antioxidant self-healing hydrogels with integrated NO-releasing behavior show great potential for treating type I diabetic wounds.