Dual-functional nano-hydroxyapatite-based dressing combats melanoma recurrence and promotes wound healing after surgery

Dual-functional nHA/CA dressing combats melanoma recurrence and promotes wound healing after surgery based on the metabolic disparities between tumor and normal cells. • The nHA/CA Gel displayed hierarchical architecture, shear-thinning injectability, self-healing properties and enhanced thermal stability. • The nHA/CA Gel exhibited cytocompatibility with normal fibroblasts, promoting their migration and proliferation through enhanced growth factor secretion, while selectively inhibited the proliferation and invasion of B16 melanoma cells, potentially mediated by Ca 2+ overload-induced cytotoxicity. • The nHA/CA Gel promoted full-thickness wound healing in SD rats by upregulating regenerative factors and resolving inflammation. • In melanoma-resected BALB/c mice, it achieved concurrent therapeutic outcomes − accelerated wound closure and reduced recurrence − via N-cadherin downregulation and apoptotic priming of residual tumor cells. Melanoma exhibits high postoperative recurrence rates due to residual tumor cells and impaired wound microenvironment prone to infection and healing dysfunction. Conventional therapeutic dressings face limitations, including complex formulations, cumbersome synthesis, and side effects, hindering clinical translation. In this study, we developed a drug-free, dual-functional dressing by integrating nHA into a chitosan-alginate (CA) matrix via dynamic hydrogen bonding and polyelectrolyte complexation. The composite hydrogel’s hierarchical architecture, stabilized by interfacial interactions between nHA surface ions and polymer chains, conferred shear-thinning injectability and self-healing properties. Crucially, metabolic disparities between tumor and normal cells drive nHA’s selective bioactivity. The nHA/CA Gel exhibited cytocompatibility with fibroblasts, promoting their migration and proliferation, likely through enhanced growth factor secretion. In contrast, it selectively inhibited the proliferation and invasion of B16 melanoma cells, potentially mediated by Ca 2+ overload-induced cytotoxicity. In vivo, the nHA/CA Gel promoted full-thickness wound healing in SD rats by upregulating regenerative factors (bFGF, EGF, PDGF) and resolving inflammation. In melanoma-resected BALB/c mice, it achieved concurrent therapeutic outcomes − accelerated wound closure and reduced recurrence − via N-cadherin downregulation and apoptotic priming of residual tumor cells. This platform addresses melanoma post-resection challenges through spatially controlled biointeractions, offering a clinically translatable strategy for melanoma wound management.