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Artificial Human Corneas: Scaffolds for Transplantation and Host Regeneration

Griffith, May Ph.D.; Hakim, Malik M.A.Sc.; Shimmura, Shigeto M.D.; Watsky, Mitchell A. Ph.D.; Li, Fengfu Ph.D.; Carlsson, David Ph.D.; Doillon, Charles J. M.D., Ph.D.; Nakamura, Masatsugu Ph.D.; Suuronen, Erik B.Sc.; Shinozaki, Naoshi Ph.D.; Nakata, Katsuhiko Ph.D.; Sheardown, Heather Ph.D.

doi: 10.1097/01.ico.0000263120.68768.f8
Invited Lecture

Purpose: To review the development of artificial corneas (pros-theses and tissue equivalents) for transplantation, and to provide recent updates on our tissue-engineered replacement corneas.

Methods: Modified natural polymers and synthetic polymers were screened for their potential to replace damaged portions of the human cornea or the entire corneal thickness. These polymers, combined with cells derived from each of the three main corneal layers or stem cells, were used to develop artificial corneas. Functional testing was performed in vitro. Trials of biocompatibility and immune and inflammatory reactions were performed by implanting the most promising polymers into rabbit corneas.

Results: Collagen-based biopolymers, combined with synthetic crosslinkers or copolymers, formed effective scaffolds for developing prototype artificial corneas that could be used as tissue replacements in the future. We have previously developed an artificial cornea that mimicked key morphologic and functional properties of the human cornea. The addition of synthetic polymers increased its toughness as it retained transparency and low light scattering, making the matrix scaffold more suitable for transplantation. These new composites were implanted into rabbits without causing any acute inflammation or immune response. We have also fabricated full-thickness composites that can be fully sutured. However, the long-term effects of these artificial corneas need to be evaluated.

Conclusions: Novel tissue-engineered corneas that comprise composites of natural and synthetic biopolymers together with corneal cell lines or stem cells will, in the future, replace portions of the cornea that are damaged. Our results provide a basis for the development of both implantable temporary and permanent corneal replacements.

University of Ottawa Eye Institute (M.G., M.H., F.L., E.S.), University of Ottawa, Ottawa, Ontario, Canada; National Research Council of Canada - ICPET (M.H., F.L., D.C.), Ottawa, Ontario, Canada; Tokyo Dental College (S.S., N.S.), Ichikawa General Hospital Cornea Center, Ichikawa, Chiba, Japan; Department of Physiology (M.A.W.), University of Tennessee Health Science Center, Memphis, Tennessee, U.S.A.; Oncology and Molecular Endocrinology Research Center (C.J.D.), Laval University, Quebec, Canada; Santen Pharmaceutical Co. Ltd. (M.N., K.N.), Nara R&D Center, Ikoma-shi, Nara, Japan; Department of Chemical Engineering (H.S.), McMaster University, Hamilton, Ontario, Canada.

Address correspondence and reprint requests to Dr. M. Griffith, University of Ottawa Eye Institute, Ottawa Hospital-General Campus, 501 Smyth Road, Ottawa, Ontario K1H 8L6, Canada. E-mail:

Grants: This work was supported by MRC-PMAC Canada grant no. PA-13983 to M.G. and C.J.D.; a Santen Pharmaceutical Co. Ltd. extramural grant to M.G. and M.A.W.; NSERC Canada Collaborative Health Research Project grants no. 227212-99 to M.G. and C.J.D., and no. 227335-99 to H.S. and M.G.; and Japanese Ministry of Education Bioventure grant to K. Tsubota, et al.; M.H. and E.S. were supported by NSERC graduate studentships.

Submitted March 26, 2002. Accepted April 26, 2002.

Copyright © 2002 Wolters Kluwer Health, Inc. All rights reserved.