Grant: Project Grant

Tissue engineering aims to create biological substitutes that are dedicated to repair or replace failing organs or tissues with natural, synthetic, or semisynthetic tissue mimics. Although tremendous developments have been reached in the production of tissue-engineered human organs, such as the skin, much remains to be done for others. Progress has been achieved in the development of living corneal substitutes produced by tissue engineering and designed to mimic the native cornea in terms of cell phenotype and tissue architecture. However, most use synthetic biomaterials combined with immortalized cells, which makes them dissimilar from the native cornea. Over the last decade, we described the production of both a 2-layer (epithelium and stroma) and 3-layer (epithelium, stroma and endothelium) human tissue-engineered cornea (hTEC) assembled using untransformed human cells grown on a totally natural stroma synthesized by living corneal fibroblasts. In this proposal, we will improve further the development of the hTEC by the addition of immune cells, and will exploit this new, three-layer hTEC supplemented with macrophages, as a model to study deeper the mechanistic of corneal wound healing. Corneal diseases are the fifth cause of blindness worldwide. As of today, it is estimated that the tremendous number of people waiting for a corneal transplantation largely exceeds that of graftable corneas available worldwide. Therefore, our three-layer hTEC supplemented with macrophages represents an outstanding biomaterial that we can use as a model to further understand the many aspects of the molecular and cellular mechanistic response of the cornea toward different types of diseases or wounds. By improving the corneal wound healing dynamic, we believe the results of this proposal will contribute at restricting the clinical progression of many corneal diseases and consequently help reduce the need for graftable donor corneas as well.