Construction of multifunctional cerium-containing nanozyme hydrogel and its component-level functions in skin wound healing.

Abstract

A multifunctional hydrogel composite incorporating cerium-based nanozymes is developed to modulate the wound microenvironment for skin regeneration. Cerium dioxide (CeO₂) nanoparticles are surface-modified with hyperbranched poly-l-lysine (HBPL), which improves their dispersion and yields a hydrated particle size of approximately 304 nm. These nanozymes are combined with glycyrrhizic acid (GA) and gelatin methacryloyl (GelMA) and crosslinked using visible light to form a CeO₂-HBPL/GA/GelMA hydrogel. The resulting material exhibits tissue adhesion, skin-like mechanical properties, and an irregular porous architecture. In vitro, the hydrogel efficiently scavenges reactive oxygen species (ROS), protects fibroblasts from oxidative damage, and inhibits Escherichia coli (E. coli) growth. It also promotes the polarization of macrophages from a pro-inflammatory (M1) to a pro-healing (M2) phenotype and enhances fibroblast proliferation. In a mouse full-thickness skin defect model, application of the hydrogel promotes wound closure, reduces scarring, and promotes complete epidermal regeneration. Histological analysis reveals decreased inflammatory infiltration and dense, organized collagen deposition resembling healthy skin. This multifunctional dressing integrates antioxidant, anti-inflammatory, and antibacterial activities, providing a proof-of-concept strategy for acute cutaneous wound repair.