Ultrasmall calcium-enriched Prussian blue nanozymes promote chronic wound healing by remodeling the wound microenvironment

Chronic wound healing remains challenging due to the oxidative microenvironment. Prussian blue (PB) nanoparticles exhibiting multiple antioxidant enzyme-like activities have attracted widespread attention, while their antioxidant efficacy remains unsatisfied. Herein, ultrasmall calcium-enriched Prussian blue nanoparticles (CaPB NPs) are simply constructed with high yields for the wound repair application. Owing to the ultrasmall size and synergistic effect of the generated dual active sites, the CaPB NPs exhibit prominent antioxidase-like activities, protecting cells from oxidative stress-induced damage. In addition to the effect of Ca on regulating keratinocyte and fibroblast growth, it has been demonstrated that the administration of CaPB NPs obviously promoted wound closure as well as collagen deposition and neovascularization in the full-thickness wound defect model in mice. Importantly, the CaPB NP treatment can effectively up-regulate the expression levels of anti-inflammatory cytokines and vascular endothelial growth factors to remodel the wound microenvironment, thereby accelerating the wound healing process. Overall, this work reveals that metal atom substitution is an effective strategy to construct ultrasmall and high-catalytic-performance PB-based nanozymes and further potentiate their effectiveness for chronic wound management.