A PVA/chitosan/gelatin scaffold incorporating salicylic acid-loaded TiO₂ nanoparticles enhances collagen I expression and accelerates cutaneous wound repair in mice.

Abstract

Wound healing is a complex biological process requiring coordinated cellular and molecular responses, motivating the development of bioactive scaffolds capable of modulating the wound microenvironment. In this study, a nanocomposite scaffold composed of chitosan, polyvinyl alcohol (PVA), and gelatin incorporating salicylic acid-loaded titanium dioxide nanoparticles (TiO₂ NPs) was fabricated and evaluated for wound-healing applications. TiO₂ nanoparticles synthesized via a co-precipitation method exhibited nanoscale dimensions, high crystallinity, a negative surface charge (-19.4 mV), and a drug-loading efficiency exceeding 90%. The scaffold showed good structural integrity under physiological conditions, excellent hemocompatibility (<5% hemolysis), and a swelling ratio of approximately 50%. Sustained, pH-independent release of salicylic acid was observed. In vitro studies demonstrated that the nanocomposite increased fibroblast migration by approximately 90% compared with untreated controls and significantly upregulated COL1 gene expression by 2.5-fold (p < 0.05), while maintaining high cell viability. In a murine excisional wound model, the nanocomposite-treated group achieved 85% wound closure by day 10, compared with 30% in untreated wounds and 50% in the drug-free scaffold group (p < 0.05), along with improved epidermal regeneration. Overall, these results indicate that controlled delivery of salicylic acid from a TiO₂-containing polymeric scaffold supports fibroblast activity, collagen-related responses, and wound closure, providing a rational basis for further optimization of multifunctional wound dressings.