Biocompatible ZnO nanoflower-infused chitosan/alginate/PVA composite for accelerated skin regeneration

Wound-healing remains a significant challenge in regenerative medicine, necessitating the development of advanced biomaterials with enhanced bioactivity and therapeutic potential. In this study, we synthesized a biocompatible zinc oxide nanoflower (ZnO NF)-infused chitosan/alginate/polyvinyl alcohol (Cs/Alg/PVA) nanocomposite for accelerated skin regeneration. ZnO NFs were synthesized via a green approach using gallic acid and ascorbic acid, yielding nanostructures with high stability and bioactive properties. The physicochemical characterization confirmed the successful formation of ZnO NFs, exhibiting a flower-like morphology. The synthesized ZnO NF-loaded Cs/Alg/PVA nanocomposite demonstrated superior swelling capacity, controlled ZnO NF release, and enhanced mechanical stability. In vitro biocompatibility studies using HDF and L929 cell lines revealed non-cytotoxic behavior and significant proliferation enhancement. Hemocompatibility assessments confirmed very minimal hemolytic activity, indicating excellent blood compatibility. In vivo, wound healing studies in a murine model demonstrated accelerated wound closure, enhanced angiogenesis, reduced inflammation, and improved collagen deposition in ZnO NF-treated groups compared to controls. Histopathological analyses further validated the superior regenerative potential of the nanocomposite. These findings highlight the promising applications of ZnO NFs-based biopolymers in advanced wound dressings, offering a multifunctional platform for tissue engineering and skin regeneration.