Glucose-activated self-cascade antibacterial and pro-angiogenesis nanozyme-functionalized chitosan-arginine thermosensitive hydrogel for chronic diabetic wounds healing

Abstract

Affected by persistent hyperglycemia, diabetic neuropathy, and vasculopathy hinder the progression of wound healing by exacerbating susceptibility to recurrent bacterial infection and impairing vascularization. In order to cater to the requirements of diabetic chronic wound healing at various stages, we designed an antibacterial and pro-angiogenic wound dressing with localized glucose-lowering capacity. In this study, we constructed a copper-based metal-organic framework (MOF) nanozyme and loaded with glucose oxidase (GOX) to prepare Cu-MOF/GOX, which was subsequently integrated with CS-Arg (chitosan modified by L-Arginine) and Pluronic (F127) to fabricate multifunctional Cu-MOF/GOX-Gel thermosensitive hydrogel. The GOX generated H₂O₂ (hydrogen peroxide) and gluconic acid by consuming high blood glucose at the wound site, thus initiating an efficient antibacterial self-cascade catalytic in the initial stages of wound healing. With the further catalysis of in situ generated H₂O₂, NO (nitric oxide) was gradually released from the hydrogel, facilitating angiogenesis and accumulation of collagen, thereby expediting subsequent phases of wound healing. Overall, the Cu-MOF/GOX-Gel exhibits a comprehensive ability to locally regulate blood glucose levels, while also synergistically promoting antibacterial activity and angiogenesis, that effectively chronic diabetic wounds healing.

Keywords: Diabetic chronic wounds; Hydrogel; Metal-organic framework (MOF); Nitric oxide; Self-cascade catalysis; Wound healing.