Oxygenated Exosome-Based Nanoeyedrop for Mitigating Hypoxia in Corneal Wound Healing: Impact on Healing Properties of Human Corneal Epithelial Cells

Abstract

The rapid and organized healing of the cornea, while maintaining optical clarity, is essential for patient health and quality of life following corneal injuries. Oxygen plays a critical role in regulating cell migration and proliferation during wound repair, and the application of stem cell-derived exosomes offers potential therapeutic benefits due to their antioxidant and antiscarring properties. In this study, we developed oxygenated exosome-coated hemoglobin nanoparticles (OExo NPs) designed for effective oxygen delivery to enhance corneal re-epithelialization, reduce inflammation, and mitigate scarring. These OExo NPs exhibit a uniform average diameter of 130 nm and demonstrate consistent oxygen release capabilities. In vitro assays using human corneal epithelial cells-transformed (HCE-T) revealed that OExo NPs significantly promote cell proliferation and accelerate migration in scratch wound assays. Fluorescence imaging confirmed the successful internalization of OExo NPs into HCE-T cells and increased intracellular oxygen levels under hypoxic conditions. Gene expression analyses indicated a downregulation of critical wound healing markers, including HIF-1α, VEGF, IL-8, and FAK, suggesting effective alleviation of hypoxia, inhibition of angiogenesis, suppression of inflammation, and reduction of scar formation. These results highlight the potential of OExo NPs as a promising therapeutic approach for topical treatment of corneal wounds.