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

Islam, M. Mirazul, Buznyk, Oleksiy, Reddy, Jagadesh C., Pasyechnikova, Nataliya, Alarcon, Emilio I., Hayes, Sally, Lewis, Philip, Fagerholm, Per, He, Chaoliang, Iakymenko, Stanislav, Liu, Wenguang, Meek, Keith Michael Andrew, Sangwan, Virender S. and Griffith, May 2018. Biomaterials-enabled cornea regeneration in patients at high risk for rejection of donor tissue transplantation. npj Regenerative Medicine 3 , 2. 10.1038/s41536-017-0038-8

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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 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 regeneration 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.

Item Type: Article
Date Type: Published Online
Status: Published
Schools: Optometry and Vision Sciences
Publisher: Nature Publishing Group
ISSN: 2057-3995
Funders: Medical Research Council
Date of First Compliant Deposit: 4 December 2017
Date of Acceptance: 12 November 2017
Last Modified: 30 Jun 2019 08:34
URI: http://orca.cf.ac.uk/id/eprint/107256

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