Research ArticleTissue Engineering

A Biosynthetic Alternative to Human Donor Tissue for Inducing Corneal Regeneration: 24-Month Follow-Up of a Phase 1 Clinical Study

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Science Translational Medicine  25 Aug 2010:
Vol. 2, Issue 46, pp. 46ra61
DOI: 10.1126/scitranslmed.3001022

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We are visual animals, and our ability to see depends on a tiny piece of transparent tissue that covers the surface of our eyes—the cornea. Constructed from parallel strands of the protein collagen, it refracts light to focus images on the retina, assisted by the adjustable lens, which modulates the focal length. The see-through nature of the cornea is easily destroyed by trauma or infection, but replacement human corneas can be inserted and reliably restore vision. The problem is that a shortage of donated corneas leaves millions of people likely to go blind. An alternative source of corneas could make a big difference. In a 2-year follow-up study of 10 patients, Fagerholm and his colleagues show that biosynthetic corneas that closely mimic the natural one are readily incorporated into the eye. They become reinnervated, restoring sensitivity to the cornea and restoring vision to the patients.

Recombinant human collagen, synthesized in yeast and chemically cross-linked, was molded into a biosynthetic cornea by the authors. They used these facsimiles to replace the distorted corneas of nine patients with keratoconus and one patient who had had a corneal infection. By monitoring the patients carefully for 2 years, they were able to see how the implants were incorporated into the existing eye. First, a normal-appearing protective layer of epithelial cells, derived from the patient, covered the surface. Then, in 9 of the 10 patients, nerves that had been cut during surgery regrew into the biosynthetic cornea, and the cornea was again sensitive to mechanical stimulation, an essential response that protects the eye from injury. Because the cornea must be transparent, it has no blood supply and oxygen must come from the film of tears that bathes the tissue. This essential element was also restored, with the tears having normal osmolarity.

Although without corrective contact lenses, the 10 patients on average did not have as good visual acuity 2 years after receiving their implants as did a group of patients with donated human corneas, with contact lenses (which they could not wear before surgery) the 10 patients’ vision was equivalent. The authors suggest that lessons learned in this initial trial will improve the vision of the next set of patients to receive the biosynthetic implants. The sutures used in this study caused problems with the epithelialization process, blocking cell migration and inducing haziness, as well as causing roughness on the surface. Less disruptive sutures should correct this problem.

These biosynthetic—but also biomimetic—corneas may soon allow many patients who need corneal transplants but do not have donors to regain normal sight.


  • * These authors contributed equally to this work.

  • Citation: P. Fagerholm, N. S. Lagali, K. Merrett, W. B. Jackson, R. Munger, Y. Liu, J. W. Polarek, M. Söderqvist, M. Griffith, A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study.Sci. Transl. Med. 2, 46ra61 (2010).

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