A Chitosan-Based Neuropeptide Hydrogel with Zinc Oxide-Assisted Antioxidant Activity for Ultraviolet B-Induced Delayed Wound Repair.

Abstract

Chronic and delayed-healing wounds are often sustained by persistent inflammation and oxidative stress, which impair cell migration, angiogenesis, and tissue remodeling. In this study, we developed a chitosan (CS)-based neuropeptide hydrogel that combines local delivery of substance P (SP) with ZnO-assisted antioxidant activity. SP was grafted onto CS, and the self-assembling peptide Nap-β was introduced to form a fibrillar hydrogel network for local retention of SP-related components. ZnO nanoparticles were incorporated to reinforce the hydrogel structure and improve antioxidant protection. The resulting CS-SP-Nap-β@ZnO hydrogel showed appropriate gelation behavior, an interconnected porous morphology, self-healing properties, sustained release behavior, and acceptable cytocompatibility and hemocompatibility. In vitro, the hydrogel reduced inflammatory cytokine production, promoted macrophage transition toward a reparative phenotype, attenuated reactive oxygen species accumulation and oxidative injury, and supported the proliferation and migration of wound-related cells. In an ultraviolet B-induced delayed-healing wound model, CS-SP-Nap-β@ZnO accelerated wound closure and promoted re-epithelialization, collagen deposition, and neovascularization. These findings suggest that CS-SP-Nap-β@ZnO can improve the wound repair microenvironment by combining SP-mediated inflammatory regulation with ZnO-assisted oxidative stress control.

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