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NPJ Regen Med. 2018 Jan 31;3:2. doi: 10.1038/s41536-017-0038-8. eCollection 2018.

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

Author information

1
1Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
2
2Schepens Eye Research Institute and Massachusetts Eye and Ear Infirmary, Harvard Medical School, Boston, MA USA.
3
Filatov Institute of Eye Diseases and Tissue Therapy of the NAMS of Ukraine, Odessa, Ukraine.
4
4Tej Kohli Cornea Institute, LV Prasad Eye Institute, Hyderabad, India.
5
5Division of Cardiac Surgery, University of Ottawa Heart Institute, Ottawa, ON Canada.
6
6School of Optometry and Vision Sciences College of Biomedical and Life Sciences, Cardiff University, Cardiff, UK.
7
7Cardiff Institute for Tissue Engineering and Repair (CITER), Cardiff University, Cardiff, UK.
8
8Key Laboratory of Polymer Eco-materials, Changchun Institute of Applied Chemistry, Chinese Academy of Sciences, Changchun, China.
9
9School of Materials Science and Engineering, Tianjin University, Tianjin, China.
10
10Department of Ophthalmology and Maisonneuve-Rosemont Hospital Research Centre, University of Montreal, Montreal, Canada.
#
Contributed equally

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.

Conflict of interest statement

The Ottawa Hospital Research Inst., Canada has filed a biomaterials patent for collagen-MPC implants licensed to Eyegenix, USA and LinkoCare, Sweden.

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