A Human Cornea-on-A-Chip for the Study of Epithelial Wound Healing by Extracellular Vesicles

Organs-on-chips are microfluidic devices for cell culturing to simulate tissue- or organ-level physiology and recapitulate their microenvironment, providing novel and significant solutions other than traditional animal tests. In vitro testing platforms for ocular biological studies have been increasingly used in preclinical efficacy and toxicity evaluation and prediction. Human cornea functions as a primary site of human eye exposure to environmental agents, requiring to establish a fully integrated cornea chip to study its biological characteristics. Here, we developed a microfluidic platform to mimic the human cornea and the complexity of its interface to the external environment. Our model consists of human corneal cells and a porous membrane embedded in the microfluidic platform, replicating the multi-scale structural organization and biological phenotype. Using this biomimetic system, we discovered and verified the fully integrated human cornea's barrier effects on the chip. Moreover, we developed an in vitro model of the corneal epithelial wound to understand cell-free therapy's efficacy using extracellular vesicles. We found that EVs derived from bone marrow-derived mesenchymal stem cells can significantly accelerate the corneal epithelial wound healing, and the decreased expression of matrix metallopeptidase 2 protein indicated that this method effectively inhibits corneal inflammation and angiogenesis. This work improves our ability to simulate the interaction between the human cornea and the external world in vitro and contribute to the future development of new screening platforms for biopharmaceuticals.