Versatile conductive hydrogel orchestrating neuro-immune microenvironment for rapid diabetic wound healing through peripheral nerve regeneration

Abstract

Diabetic wound (DW), notorious for prolonged healing processes due to the unregulated immune response, neuropathy, and persistent infection, poses a significant challenge to clinical management. Current strategies for treating DW primarily focus on alleviating the inflammatory milieu or promoting angiogenesis, while limited attention has been given to modulating the neuro-immune microenvironment. Thus, we present an electrically conductive hydrogel dressing and identify its neurogenesis influence in a nerve injury animal model initially by encouraging the proliferation and migration of Schwann cells. Further, endowed with the synergizing effect of near-infrared responsive release of curcumin and nature-inspired artificial heterogeneous melanin nanoparticles, it can harmonize the immune microenvironment by restoring the macrophage phenotype and scavenging excessive reactive oxygen species. This in-situ formed hydrogel also exhibits mild photothermal therapy antibacterial efficacy. In the infected DW model, this hydrogel effectively supports nerve regeneration and mitigates the immune microenvironment, thereby expediting the healing progress. The versatile hydrogel exhibits significant therapeutic potential for application in DW healing through fine-tuning the neuro-immune microenvironment.

Keywords: Curcumin release; Diabetic wounds; Hydrogel dressing; Nerve repair; Neuro-immune microenvironmental modulation.