A simple, cross-linked collagen tissue substitute for corneal implantation

Yuwen Liu, Lisha Gan, David J. Carlsson, Per Fagerholm, Neil Lagali, Mitchell Aaron Watsky, Rejean Munger, William G. Hodge, David Priest, May Griffith

Research output: Contribution to journalArticle

143 Citations (Scopus)

Abstract

PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%; pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations.

Original languageEnglish (US)
Pages (from-to)1869-1875
Number of pages7
JournalInvestigative Ophthalmology and Visual Science
Volume47
Issue number5
DOIs
StatePublished - May 1 2006

Fingerprint

Cornea
Collagen
Rabbits
Swine
Ethyldimethylaminopropyl Carbodiimide
Collagen Type X
Cross-Linking Reagents
Miniature Swine
Carbodiimides
Refractometry
Corneal Transplantation
Touch
Tears
Confocal Microscopy
Regeneration
Emergencies
Transplantation
Transplants
Water
Proteins

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

Cite this

A simple, cross-linked collagen tissue substitute for corneal implantation. / Liu, Yuwen; Gan, Lisha; Carlsson, David J.; Fagerholm, Per; Lagali, Neil; Watsky, Mitchell Aaron; Munger, Rejean; Hodge, William G.; Priest, David; Griffith, May.

In: Investigative Ophthalmology and Visual Science, Vol. 47, No. 5, 01.05.2006, p. 1869-1875.

Research output: Contribution to journalArticle

Liu, Y, Gan, L, Carlsson, DJ, Fagerholm, P, Lagali, N, Watsky, MA, Munger, R, Hodge, WG, Priest, D & Griffith, M 2006, 'A simple, cross-linked collagen tissue substitute for corneal implantation', Investigative Ophthalmology and Visual Science, vol. 47, no. 5, pp. 1869-1875. https://doi.org/10.1167/iovs.05-1339
Liu, Yuwen ; Gan, Lisha ; Carlsson, David J. ; Fagerholm, Per ; Lagali, Neil ; Watsky, Mitchell Aaron ; Munger, Rejean ; Hodge, William G. ; Priest, David ; Griffith, May. / A simple, cross-linked collagen tissue substitute for corneal implantation. In: Investigative Ophthalmology and Visual Science. 2006 ; Vol. 47, No. 5. pp. 1869-1875.
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AU - Liu, Yuwen

AU - Gan, Lisha

AU - Carlsson, David J.

AU - Fagerholm, Per

AU - Lagali, Neil

AU - Watsky, Mitchell Aaron

AU - Munger, Rejean

AU - Hodge, William G.

AU - Priest, David

AU - Griffith, May

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N2 - PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%; pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations.

AB - PURPOSE. To develop a simple corneal substitute from crosslinked collagen. METHODS. Porcine type I collagen (10%; pH 5), was mixed with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and N-hydroxysuccinimide (NHS). The final homogenous solution was molded to corneal dimensions, cured, and then implanted into rabbits and minipigs by lamellar keratoplasty. The implants were followed for up to 6 months after surgery. Clinical examinations of the cornea included detailed slit lamp biomicroscopy, in vivo confocal microscopy, topography and esthesiometry for nerve function. Histopathologic examinations were also performed on rabbit corneas harvested after 6 months. RESULTS. Cross-linked collagen (refractive index, 1.35) had optical clarity superior to human corneas. Implanted into rabbit and porcine corneas, only 1 of 24 of the surgical corneas showed a slight haze at 6 months after surgery. All other implants showed no adverse reactions and remained optically clear. Topography showed a smooth surface and a profile similar to that of the contralateral nonsurgical eye. The implanted matrices promoted regeneration of corneal cells, tear film, and nerves. Touch sensitivity was restored, indicating some restoration of function. The corneas with implants showed no significant loss of thickness and demonstrated stable host- graft integration. CONCLUSIONS. Collagen can be adequately stabilized, using water soluble carbodiimides as protein cross-linking reagents, in the fabrication of corneal matrix substitutes for implantation. The simple cross-linking methodology would allow for easy fabrication of matrices for transplantation in centers where there is a shortage of corneas, or where there is need for temporary patches to repair perforations in emergency situations.

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