Recombinant human collagen for tissue engineered corneal substitutes

Wenguang Liu; Kimberley Merrett; May Griffith; Per Fagerholm; Subhadra Dravida; Belinda Heyne; Juan C. Scaiano; Mitchell A. Watsky; Naoshi Shinozaki; Neil Lagali; Rejean Munger; Fengfu Li

doi:10.1016/j.biomaterials.2007.11.011

Recombinant human collagen for tissue engineered corneal substitutes

Wenguang Liu, Kimberley Merrett, May Griffith, Per Fagerholm, Subhadra Dravida, Belinda Heyne, Juan C. Scaiano, Mitchell A. Watsky, Naoshi Shinozaki, Neil Lagali, Rejean Munger, Fengfu Li

Research output: Contribution to journal › Article › peer-review

200 Scopus citations

Abstract

We successfully fabricated transparent, robust hydrogels as corneal substitutes from concentrated recombinant human type I and type III collagen solutions crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). White light transmission through these gels is comparable or superior to that of human corneas. Hydrogels from both type I and type III collagens supported in vitro epithelium and nerve over-growth. While both these biocompatible hydrogels have adequate tensile strength and elasticity for surgical manipulation, type III collagen hydrogels tended to be mechanically superior. Twelve-month post-implantation results of type I recombinant collagen-based corneal substitutes into mini-pigs showed retention of optical clarity, along with regeneration of corneal cells, nerves and tear film. For clinical use, implants based on fully characterized, recombinant human collagen eliminate the risk of pathogen transfer or xenogeneic immuno-responses posed by animal collagens.

Original language	English (US)
Pages (from-to)	1147-1158
Number of pages	12
Journal	Biomaterials
Volume	29
Issue number	9
DOIs	https://doi.org/10.1016/j.biomaterials.2007.11.011
State	Published - Mar 2008
Externally published	Yes

Keywords

Cornea regeneration
Cornea transplantation
Corneal substitute
Hydrogel
Recombinant human collagen

ASJC Scopus subject areas

Biophysics
Bioengineering
Ceramics and Composites
Biomaterials
Mechanics of Materials

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10.1016/j.biomaterials.2007.11.011

Cite this

@article{e0a8f3053dca42ae905bddfea0c684d4,

title = "Recombinant human collagen for tissue engineered corneal substitutes",

abstract = "We successfully fabricated transparent, robust hydrogels as corneal substitutes from concentrated recombinant human type I and type III collagen solutions crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). White light transmission through these gels is comparable or superior to that of human corneas. Hydrogels from both type I and type III collagens supported in vitro epithelium and nerve over-growth. While both these biocompatible hydrogels have adequate tensile strength and elasticity for surgical manipulation, type III collagen hydrogels tended to be mechanically superior. Twelve-month post-implantation results of type I recombinant collagen-based corneal substitutes into mini-pigs showed retention of optical clarity, along with regeneration of corneal cells, nerves and tear film. For clinical use, implants based on fully characterized, recombinant human collagen eliminate the risk of pathogen transfer or xenogeneic immuno-responses posed by animal collagens.",

keywords = "Cornea regeneration, Cornea transplantation, Corneal substitute, Hydrogel, Recombinant human collagen",

author = "Wenguang Liu and Kimberley Merrett and May Griffith and Per Fagerholm and Subhadra Dravida and Belinda Heyne and Scaiano, {Juan C.} and Watsky, {Mitchell A.} and Naoshi Shinozaki and Neil Lagali and Rejean Munger and Fengfu Li",

note = "Funding Information: Supported by an NSERC Canada strategic projects grant #246418-01 to MG and MAW. The authors thank Dr. Y. Kato, TDC Cornea Centre and Eye Bank, Japan and Mr. Fukuda, Kyorin University, Japan for cornea TEMs; Lea Muzakare, Dr. Marilyn Keaney and her team at University of Ottawa for excellent veterinary services and care of animals; Dr. Chao Deng's help on revising some figures. Thanks also to CooperVision for their financial supplementation of the animal implantation study.",

year = "2008",

month = mar,

doi = "10.1016/j.biomaterials.2007.11.011",

language = "English (US)",

volume = "29",

pages = "1147--1158",

journal = "Biomaterials",

issn = "0142-9612",

publisher = "Elsevier BV",

number = "9",

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TY - JOUR

T1 - Recombinant human collagen for tissue engineered corneal substitutes

AU - Liu, Wenguang

AU - Merrett, Kimberley

AU - Griffith, May

AU - Fagerholm, Per

AU - Dravida, Subhadra

AU - Heyne, Belinda

AU - Scaiano, Juan C.

AU - Watsky, Mitchell A.

AU - Shinozaki, Naoshi

AU - Lagali, Neil

AU - Munger, Rejean

AU - Li, Fengfu

N1 - Funding Information: Supported by an NSERC Canada strategic projects grant #246418-01 to MG and MAW. The authors thank Dr. Y. Kato, TDC Cornea Centre and Eye Bank, Japan and Mr. Fukuda, Kyorin University, Japan for cornea TEMs; Lea Muzakare, Dr. Marilyn Keaney and her team at University of Ottawa for excellent veterinary services and care of animals; Dr. Chao Deng's help on revising some figures. Thanks also to CooperVision for their financial supplementation of the animal implantation study.

PY - 2008/3

Y1 - 2008/3

N2 - We successfully fabricated transparent, robust hydrogels as corneal substitutes from concentrated recombinant human type I and type III collagen solutions crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). White light transmission through these gels is comparable or superior to that of human corneas. Hydrogels from both type I and type III collagens supported in vitro epithelium and nerve over-growth. While both these biocompatible hydrogels have adequate tensile strength and elasticity for surgical manipulation, type III collagen hydrogels tended to be mechanically superior. Twelve-month post-implantation results of type I recombinant collagen-based corneal substitutes into mini-pigs showed retention of optical clarity, along with regeneration of corneal cells, nerves and tear film. For clinical use, implants based on fully characterized, recombinant human collagen eliminate the risk of pathogen transfer or xenogeneic immuno-responses posed by animal collagens.

AB - We successfully fabricated transparent, robust hydrogels as corneal substitutes from concentrated recombinant human type I and type III collagen solutions crosslinked with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide (EDC) and N-hydroxysuccinimide (NHS). White light transmission through these gels is comparable or superior to that of human corneas. Hydrogels from both type I and type III collagens supported in vitro epithelium and nerve over-growth. While both these biocompatible hydrogels have adequate tensile strength and elasticity for surgical manipulation, type III collagen hydrogels tended to be mechanically superior. Twelve-month post-implantation results of type I recombinant collagen-based corneal substitutes into mini-pigs showed retention of optical clarity, along with regeneration of corneal cells, nerves and tear film. For clinical use, implants based on fully characterized, recombinant human collagen eliminate the risk of pathogen transfer or xenogeneic immuno-responses posed by animal collagens.

KW - Cornea regeneration

KW - Cornea transplantation

KW - Corneal substitute

KW - Hydrogel

KW - Recombinant human collagen

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Recombinant human collagen for tissue engineered corneal substitutes

Abstract

Keywords

ASJC Scopus subject areas

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