Enhanced Wound Healing and Anti-Inflammatory Effects of Vitamin C-Loaded Hyaluronic Acid–Collagen Scaffolds in Preclinical Rat Models

Wound healing is a complex biological process critical for restoring skin integrity after injury. However, chronic wounds present significant clinical challenges due to persistent inflammation, disrupted collagen synthesis, and susceptibility to infection. Bioactive scaffolds have emerged as promising therapeutic strategies to enhance tissue regeneration by modulating cellular behavior and extracellular matrix (ECM) dynamics. This study explores a hyaluronic acid-collagen (HyCol) scaffold enriched with vitamin C (VC), producing (VC-HyCol) to improve wound healing in preclinical rat models. Hyaluronic acid and collagen, key ECM components, provide structural and biochemical support, while vitamin C acts as both a collagen biosynthesis cofactor and an antioxidant to counteract oxidative stress. The scaffold was designed to emulate the native ECM microenvironment, facilitating fibroblast proliferation, keratinocyte migration, and angiogenesis. Physicochemical characterization, biocompatibility assessments, and in vivo wound healing experiments were performed to evaluate its therapeutic efficacy. Results demonstrated that the incorporation of vitamin C significantly enhanced fibroblast activity, reduced inflammatory markers, and accelerated tissue regeneration compared to control groups. Histological and molecular analyses further confirmed enhanced collagen deposition and neovascularization, indicating faster and more organized wound repair. These findings highlight the potential of this multifunctional scaffold as an advanced wound dressing, with significant implications for regenerative medicine and clinical wound management.