Engineering FeSe ₂ @PDA-RGD Nanoplatform Integrating Redox Modulation and Immunoregulation for Enhanced Cutaneous Wound Healing

Chronic wounds are characterized by persistent oxidative stress, unresolved inflammation, and impaired tissue remodeling, posing a major clinical challenge. Here, we report a bioinspired nanoplatform—polydopamine-coated, RGD-functionalized iron diselenide nanorods (FeSe 2 @PDA-RGD)—engineered to integrate antioxidant activity with immunoregulatory and pro-healing functions. FeSe 2 nanorods serve as a sustained donor to support endogenous redox defense, while PDA enhances colloidal stability and biocompatibility, and surface RGD motifs promote cell adhesion and integrin-mediated crosstalk. Comprehensive physicochemical characterizations confirmed successful functionalization and stable nanostructures. In vitro, FeSe 2 @PDA-RGD effectively scavenged reactive oxygen species, reprogrammed macrophages toward an anti-inflammatory M2 phenotype, and modulated cytokine secretion Macrophage–endothelial coculture demonstrated enhanced HUVEC migration and VEGF expression, while macrophage–fibroblast coculture revealed increased fibroblast proliferation and migration. In vivo, FeSe 2 @PDA-RGD accelerated wound closure in a full-thickness murine skin model without detectable systemic toxicity, as evidenced by stable body weight, normal serum biochemistry, hematology, and intact histology of major organs. Collectively, FeSe 2 @PDA-RGD establishes a favorable immune–redox microenvironment that promotes angiogenesis and tissue regeneration, highlighting its translational potential as an advanced therapeutic for chronic wound healing.