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.

Corneas with severe pathologies have a high risk of rejection when conventionally grafted with human donor tissues. In this early observational study, we grafted bioengineered corneal implants made from recombinant human collagen and synthetic phosphorylcholine polymer into three patients for whom donor cornea transplantation carried a high risk of transplant failure. These patients suffered from corneal ulcers and recurrent erosions preoperatively. The implants provided relief from pain and discomfort, restored corneal integrity by promoting endogenous regeneration of corneal tissues, and improved vision in two of three patients. Such implants could in the future be alternatives to donor corneas for high-risk patients, and therefore, merits further testing in a clinical trial.

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We have previously shown that recombinant human collagen (RHC)‐based hydrogels fabricated into cell‐free corneal implants are able to induce regeneration of the corneas of 10 patients in a Phase 1 clinical study. At four years post‐operative, all implants were stably integrated without the use of sustained immunosuppression. Corneal tissue and nerves were regenerated. For use in high risk corneal transplantation such as burns and cases of persistent, non‐infectious ulcers, we had reinforced the collagen implants with a second network of synthetic phosphorylcholine to form a hydogel comprising of interpenetratig networks of collagen‐phosphorylcholine (RHC‐MPC). In a pilot study within a hospital setting, in accordance to the Declaration of Helsinki, with ethical permission and informed consent, four patients were grafted with cell‐free RHC‐MPC implants after manual excision of the ulcerated areas. After six to 12 months post‐grafting, all implanted corneas had a stable epithelium and visual acuity improved 1‐2 lines compared to pre‐operative levels. Our pilot study shows RHC‐MPC implants are safe in patients and appeared to withstand the adverse microenvironment within the corneas with severe pathology and high risk of rejection.

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