A human cornea-on-a-chip for the study of epithelial wound healing by extracellular vesicles

Highlights

• Combined human corneal cells and microfluidics to mimic ocular surface in vitro

• Integrated human cornea’s barrier effects on the microfluidic platform

• In vitro model of mild corneal epithelial wound to test cell-free therapeutics

• Extracellular vesicles accelerate corneal epithelial wound healing

Summary

Organs-on-chips are microfluidic devices for cell culturing to simulate tissue-level or organ-level physiology and recapitulate their microenvironment, providing new 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 prediction. Here, we developed a microfluidic platform consisting of human corneal cells and porous membrane, replicating the multi-scale structural organization and biological phenotype. We verified the fully integrated human cornea’s barrier effects on the chip. Moreover, we found that extracellular vesicles derived from bone marrow-derived mesenchymal stem cells can significantly accelerate the mild 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 contributes to the future development of new screening platforms for biopharmaceuticals.