Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation

Abstract

The severe worldwide shortage of donor organs, and severe pathologies placing patients at high risk for rejecting conventional cornea transplantation, have left many corneal blind patients untreated. Following successful pre-clinical evaluation in mini-pigs, we tested a biomaterials-enabled pro-regeneration strategy to restore corneal integrity in an open-label observational study of six patients. Cell-free corneal implants comprising recombinant human collagen and phosphorylcholine were grafted by anterior lamellar keratoplasty into corneas of unilaterally blind patients diagnosed at high-risk for rejecting donor allografts. They were followed-up for a mean of 24 months. Patients with acute disease (ulceration) were relieved of pain and discomfort within 1–2 weeks post-operation. Patients with scarred or ulcerated corneas from severe infection showed better vision improvement, followed by corneas with burns. Corneas with immune or degenerative conditions transplanted for symptom relief only showed no vision improvement overall. However, grafting promoted nerve regeneration as observed by improved touch sensitivity to near normal levels in all patients tested, even for those with little/no sensitivity before treatment. Overall, three out of six patients showed significant vision improvement. Others were sufficiently stabilized to allow follow-on surgery to restore vision. Grafting outcomes in mini-pig corneas were superior to those in human subjects, emphasizing that animal models are only predictive for patients with non-severely pathological corneas; however, for establishing parameters such as stable corneal tissue and nerve regeneration, our pig model is satisfactory. While further testing is merited, we have nevertheless shown that cell-free implants are potentially safe, efficacious options for treating high-risk patients.

Biosynthetic corneas improve vision

A biomaterial implant supports the regeneration of severely damaged corneas in patients at high risk for rejecting conventional transplantation. An international team from Canada, China, India, Sweden, Ukraine and United Kingdom used mini-pigs to confirm the safety of implanting cell-free corneas made from recombinant human collagen and a synthetic lipid, before examining the effects of implantation on human vision in seven patients. The implants were well-tolerated and led to significant vision improvement in patients with damaged corneas due to infection. Furthermore, within two weeks of surgery the implants had relieved pain. Over two years, sensitivity to touch improved, suggesting an ability to promote nerve regeneration. This study supports the use of animal models to test biomaterials designed for medical applications and describes a safe and promising option for treating patients that not treatable by conventional corneal transplantation.