Bioartificial human corneas generated by tissue engineering. A historical and technical review.

using synthetic or natural biomaterials, especially collagen, fibrin, and agarose. Cells and biomaterials are combined with bioactive factors, inducing cell proliferation and differentiation. A review of previous studies revealed that most bioartificial corneas were not able to fulfill the complex requirements required for clinical translation, which include a thorough preclinical characterization, generation of the tissue as an advanced therapy medicinal product, a clinical research phase, and a final authorization by the European Medicines Agency or another competent regulatory agency. Most authorized products correspond to partial corneal substitutes consisting of one cell type associated or not with a scaffold, and only one product consisting of a human bioartificial cornea containing a fibrin-agarose scaffold and two corneal cell lineages (epithelial and stromal cells) called NANOULCOR was evaluated in patients in the context of an advanced therapy medicinal product. These findings confirm the existence of a bottleneck between basic and clinical research and suggest the need to implement novel clinical studies to develop new therapies that can improve the results of current corneal therapies.