Regenerative medicine for the corneal endothelium: self-unfolding, thermo-responsive bioengineered corneal grafts

For many patients with corneal diseases, a corneal transplant is the only available treatment option to prevent blindness. Most of the patients that need a corneal transplant suffer from corneal diseases that only affect the inner layer of the cornea, namely the endothelial cell layer and their associated basement membrane. Replacing just this inner layer by healthy endothelial donor cells on a membrane can effectively restore the patient's vision. Due to a worldwide shortage of corneal donor tissue, however, thousands of patients do not receive the much needed transplant.
A solution to this transplant shortage is to ‘build’ corneal transplants in the lab. For this approach, corneal endothelial cells are prepared in large quantities from induced pluripotent stem cells and placed on a bio-engineered membrane that resembles in many ways the natural membrane. Since the membrane is bio-engineered, additional properties that the natural membrane does not have, can be added. In this project we work with a membrane that, at temperatures below the body temperature, is rolled up like a natural thin corneal transplant, but unfolds by itself when exposed to body temperature after injection into the anterior chamber of the eye. The graft unfolding step is one of the most challenging steps during a corneal transplantation and with this new property we expect the surgery to be much less demanding and therefore more accessible to corneal surgeons. In this project, we will optimize the bioengineered grafts and test them surgically in the lab which is an important step towards the clinical testing of these new type of transplants.