COBRAS

The aim of this project is to establish a French consortium to produce 3D-printed corneal epithelial-stromal equivalents compatible with Good Manufacturing Practises (GMP), suitable for corneal grafting. These printed corneas will be produced using allogenic corneal epithelial cells and corneal or umbilical cord mesenchymal stromal cells as the source of the stromal cells.
Current cell therapies for corneal disorders generally focus on epithelial or stromal components separately. However, the epithelial compartment cannot survive on a defective stroma. Long-term results of epithelial cell therapies in severely affected corneas show that purely epithelial grafts ultimately require stromal replacement, such as keratoplasty, as they cannot establish themselves durably on a diseased stroma. Currently epithelial-stromal composites have not yet been proposed for human corneal reconstruction. Therefore, this project aims to create self-supporting, 3D-printed epithelial-stromal composites to overcome limbal stem cell deficiencies and/or treat corneal ulcerations. These composites are expected to correct pathological scarring, neovascularization and reduce/prevent associated inflammation. These bioengineered corneal equivalents will also prevent corneal fibrosis by grafting a maturing basement membrane and reduce corneal irregularities by replacing the melted stroma. The ability to print and cryoconserve large sheets of epithelial-stromal equivalents promises to revolutionize the management of corneal disorders leading to blindness, by directly addressing ulceration and visual rehabilitation, while significantly reducing production time and costs while increasing the availability of these treatments in clinical settings in a context of graft shortages. Corneal bioequivalents will be also available for experimental pharmacological and toxicological models for advanced biotherapies such as extracellular vesicles and chemotherapy-conjugated antibodies. The consortium is composed of experts in GMP-compliant bioprinting, cryopreservation, translational research, and experimental corneal surgery. These teams have a proven track record in these fields and already have the infrastructure and skills needed to execute the COBRAS program, thereby limiting the risks associated with such an innovative project.