Tissue-engineered recombinant human collagen-based corneal substitutes for implantation: performance of type I versus type III collagen.
OBJECTIVE
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.
University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
Kimberley
K
Merrett
Per
P
Fagerholm
Christopher R
CR
McLaughlin
Subhadra
S
Dravida
Neil
N
Lagali
Naoshi
N
Shinozaki
Mitchell A
MA
Watsky
Rejean
R
Munger
Yasuhiro
Y
Kato
Fengfu
F
Li
Christopher J
CJ
Marmo
May
M
Griffith
D001187:Artificial Organs / Q000706:statistics & numerical data*; D001672:Biocompatible Materials / Q000737:chemistry*; D001696:Biomechanical Phenomena; D003094:Collagen / Q000502:physiology*; D024042:Collagen Type I / Q000235:genetics*; D024061:Collagen Type III / Q000235:genetics*; D003315:Cornea / Q000502:physiology*; D016039:Corneal Transplantation / Q000379:methods*; D006801:Humans; D011994:Recombinant Proteins; D012031:Refractometry; D013718:Tensile Strength; D023822:Tissue Engineering / Q000379:methods
D001672:Biocompatible Materials; D024042:Collagen Type I; D024061:Collagen Type III; D011994:Recombinant Proteins; D003094:Collagen