Enhancement of wound healing through chitosan/gelatin/polyvinyl alcohol-based nanocomposites containing chrysin-loaded cerium oxide nanoparticles: a synergistic approach to tissue regeneration

Chronic and infected wounds remain a significant clinical challenge, requiring advanced therapeutic strategies to accelerate repair and improve outcomes. This study developed a chitosan/gelatin/polyvinyl alcohol (CS/GEL/PVA) nanocomposite incorporating chrysin-loaded cerium oxide nanoparticles (CeO₂@Chry) to connect their antioxidant, anti-inflammatory, and regenerative properties for enhanced wound healing. CeO₂ nanoparticles were synthesized <i>via</i> a green method, loaded with chrysin, and embedded into a polymeric matrix to form a stable, transparent, and flexible dry film. Physicochemical characterization revealed uniform morphology, high swelling capacity (∼80%), and strong structural integrity. Hemolysis assays confirmed excellent hemocompatibility, and MTT-based cytotoxicity tests on human dermal fibroblasts (HDF) and murine fibroblasts (L929) demonstrated good biocompatibility up to 500 µg/mL. Proliferation and scratch assays indicated dose-dependent stimulation of fibroblast growth and migration, with the 1 mg/mL formulation exhibiting the greatest effect. Notably, treatment significantly upregulated Col1 gene expression, indicating potential in promoting extracellular matrix synthesis. <i>In vivo</i> evaluation using a murine excisional wound model demonstrated accelerated wound closure, improved tissue regeneration, enhanced angiogenesis, complete re-epithelialization, and reduced inflammation in CeO₂@Chry-treated wounds compared to controls. These findings suggest that the CS/GEL/PVA/CeO₂@Chry nanocomposite is a biocompatible, multifunctional wound dressing with strong potential for managing both acute and chronic skin injuries. Its combined antioxidant, anti-inflammatory, and pro-regenerative actions make it a promising candidate for clinical translation in advanced wound care.