Sustainable Wound Healing Using Riboflavin-EnhancedChitosan-Graphene Oxide Nanocomposites

Abstract

Wound healing is a complex and regulated biological process in which hypoxic conditions in wounds delay tissue repair and promote bacterial infection. While nanotechnology-based oxygen-releasing materials (ORMs) mitigate hypoxia by enhancing collagen synthesis, angiogenesis, and cell proliferation, conventional ORMs suffer from cytotoxicity, limited biodegradability, and reactive radical overproduction. This study introduces riboflavin as a bioderived ORM alternative. Riboflavin acts as a photosensitizer, generating controlled reactive oxygen species, while providing antimicrobial, antioxidant, and anti-inflammatory benefits. We engineered a nanocomposite combining riboflavin with chitosan and graphene oxide for structural reinforcement. Characterization via FTIR, XRD, Raman, TM-AFM, FE-SEM, and FE-TEM confirmed successful integration with enhanced thermal stability (up to 700 °C) and skin-adhesive properties. The composite forms a flexible dried patch or gel, exhibiting responsive swelling (5–24-fold at pH 7) for exudate absorption. Cytotoxicity assays using human dermal fibroblast and rat fibroblast showed >80% cell viability (p < 0.05). Riboflavin enrichment boosted antibacterial efficiency, achieving a 20-fold reduction against S. aureus and P. aeruginosa within 24 h. Scratch assays revealed accelerated fibroblast migration, with 81% wound closure in 18 h and complete healing by 24 h. By combining hypoxia alleviation, infection control, and cytocompatibility, the nanocomposite overcomes the key limitations of traditional ORMs, offering a sustainable strategy for wound care.