Tissue-engineered recombinant human collagen-based corneal substitutes for implantation: Performance of type I versus type III collagen

Kimberley Merrett, Per Fagerholm, Christopher R. McLaughlin, Subhadra Dravida, Neil Lagali, Naoshi Shinozaki, Mitchell A. Watsky, Rejean Munger, Yasuhiro Kato, Fengfu Li, Christopher J. Marmo, May Griffith

Research output: Contribution to journalArticlepeer-review

101 Scopus citations


PURPOSE. To compare the efficacies of recombinant human collagens types I and III as corneal substitutes for implantation. METHODS. Recombinant human collagen (13.7%) type I or III was thoroughly mixed with 1-ethyl-3-(3- dimethylaminopropyl) carbodiimide and N-hydroxysuccinimide. The final homogenous solution was either molded into sheets for in vitro studies or into implants with the appropriate corneal dimensions for transplantation into minipigs. Animals with implants were observed for up to 12 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, and fundus examination. Histopathologic examinations were also performed on corneas harvested after 12 months. RESULTS. Both cross-linked recombinant collagens had refractive indices of 1.35, with optical clarity similar to that in human corneas. Their chemical and mechanical properties were similar, although RHC-III implants showed superior optical clarity. Implants into pig corneas over 12 months show comparably stable integration, with regeneration of corneal cells, tear film, and nerves. Optical clarity was also maintained in both implants, as evidenced by fundus examination. CONCLUSIONS. Both RHC-I and -III implants can be safely and stably integrated into host corneas. The simple cross-linking methodology and recombinant source of materials makes them potentially safe and effective future corneal matrix substitutes.

Original languageEnglish (US)
Pages (from-to)3887-3894
Number of pages8
JournalInvestigative Ophthalmology and Visual Science
Issue number9
StatePublished - Sep 2008
Externally publishedYes

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience


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