Successful development and clinical translation of a novel anterior lamellar artificial cornea.

Blindness due to corneal diseases is a common pathology affecting up to 23 million individuals worldwide. The gold-standard treatment is donor corneal transplantation, which is associated to different levels of morbidity. A novel approach involving the tissue engineering field, is use of bioartificial human organs. We describe the successful clinical translation of a novel tissue-engineered anterior human cornea, which is currently being tested in a phase I/II clinical trial to treat severe corneal trophic ulcers with preliminary good feasibility and safety results.This bioartificial cornea is based on a nanostructured fibrin-agarose biomaterial containing human allogeneic stromal keratocytes and cornea epithelial cells, mimicking the human native anterior cornea in terms of optical, mechanical and biological behavior. This product is manufactured as a clinical grade Tissue Engineering Product, fulfilling European requirements and regulations.The clinical translation process included several phases: an initial in vitro and in vivo preclinical research plan, including preclinical advice from the Spanish Medicines Agency followed by additional preclinical development, the adaptation of the biofabrication protocols to a GMP manufacturing process, including all quality controls required, as well as the design of an advanced therapy clinical trial.The experimental development and successful translation of ATMPs for clinical application has to overcome many obstacles, especially when undertaken by academia or SMEs. We expect that our experience and research strategy may help future researchers to efficiently transfer their preclinical results into the clinical settings.