Nanxin Zhang, Bendian Song, Rongtao Cui
Chronic wounds are difficult to heal due to pathological microenvironments characterized by persistent inflammation, oxidative stress, hypoxia, and biofilm infections; traditional therapies are unable to comprehensively address these issues. Nanomaterials, with their unique physicochemical properties, bring about a paradigm shift in treatment by regulating the wound microenvironment through multi-target mechanisms. This review comprehensively analyzes the latest advances in metallic, carbon-based, polymeric, and composite nanomaterials, focusing on how these materials effectively treat chronic wounds by scavenging reactive oxygen species, inducing the polarization of macrophages from the pro-inflammatory M1 to the reparative M2 phenotype, promoting angiogenesis, and enabling controlled drug release. Emerging stimulus-responsive nanoplatforms and composite systems can synergistically remove biofilms, reduce inflammation, and remodel the extracellular matrix, achieving the dual effects of accelerated healing and scar reduction. We also discuss challenges in translation, including biosafety, pharmacokinetics, and large-scale production, and propose future directions for integration with smart drug delivery, cell therapy, and gene editing. This review provides a theoretical basis and research guidance for utilizing nanotechnology to overcome barriers to chronic wound healing and prevent pathological scarring.