Comprehensive Characterization and Sustained, On-Demand Delivery of Corneal Epithelial Extracellular Vesicles for Healing Corneal Epithelium

Extracellular vesicles (EVs) derived from corneal epithelial cells have shown great promise in promoting corneal wound healing and stromal regeneration but face challenges with rapid clearance from the eye. This study addresses this challenge by developing a sustained release platform using a biocompatible collagen-based hydrogel. We successfully isolated, purified, and characterized corneal epithelial EVs, assessed their efficacy in corneal epithelial healing in vitro, and demonstrated their sustained delivery over ten days followed by an on-demand release through enzymatic degradation of the hydrogel. To develop a microscale understanding of the EV-diffusion inside the hydrogel matrix, we probed the hydrogel network with several model compounds and nanoparticles by using advanced confocal microscopy analyses followed by fitting our results to established diffusion models. Our findings suggest this innovative approach offers a safe and effective strategy to promote corneal wound healing. This technology has the potential to revolutionize corneal injury treatment and improve patient outcomes.