Current and Future Cornea Chip Models for Advancing Ophthalmic Research and Therapeutics

Corneal blindness remains a significant global health challenge, with limited treatment options due to donor tissue scarcity outside of the United States and inadequate in vitro models. This review analyzes the current state of cornea chip technology, addressing fundamental challenges and exploring future directions. Recent advancements in biomaterials and fabrication techniques are discussed that aim to recapitulate the complex structure and function of the human cornea, including the multilayered epithelium, organized stroma, and functional endothelium. The review highlights the potential of the cornea chips to revolutionize ocular research by offering more predictive and physiologically relevant models for drug screening, disease modeling, and personalized medicine. Current designs, their applications in studying drug permeability, barrier function, and wound healing, and their limitations in replicating native corneal architecture, are examined. Key challenges include integrating corneal curvature, basement membrane formation, and innervation. Applications are explored in modeling diseases like keratitis, dry eye disease, keratoconus, and Fuchs' endothelial dystrophy. Future directions include incorporating corneal curvature using hydraulically controlled systems, using patient-derived cells, and developing comprehensive disease models to accelerate therapy development and reduce reliance on animal testing.