title: Cellular and nerve regeneration within a biosynthetic extracellular matrix for corneal transplantation.
abstract: Our objective was to determine whether key properties of extracellular matrix (ECM) macromolecules can be replicated within tissue-engineered biosynthetic matrices to influence cellular properties and behavior. To achieve this, hydrated collagen and N-isopropylacrylamide copolymer-based ECMs were fabricated and tested on a corneal model. The structural and immunological simplicity of the cornea and importance of its extensive innervation for optimal functioning makes it an ideal test model. In addition, corneal failure is a clinically significant problem. Matrices were therefore designed to have the optical clarity and the proper dimensions, curvature, and biomechanical properties for use as corneal tissue replacements in transplantation. In vitro studies demonstrated that grafting of the laminin adhesion pentapeptide motif, YIGSR, to the hydrogels promoted epithelial stratification and neurite in-growth. Implants into pigs' corneas demonstrated successful in vivo regeneration of host corneal epithelium, stroma, and nerves. In particular, functional nerves were observed to rapidly regenerate in implants. By comparison, nerve regeneration in allograft controls was too slow to be observed during the experimental period, consistent with the behavior of human cornea transplants. Other corneal substitutes have been produced and tested, but here we report an implantable matrix that performs as a physiologically functional tissue substitute and not simply as a prosthetic device. These biosynthetic ECM replacements should have applicability to many areas of tissue engineering and regenerative medicine, especially where nerve function is required.
authors.affiliation: University of Ottawa Eye Institute, Ottawa, Ontario, Canada K1H 8L6.
authors.forename: Fengfu
authors.initials: F
authors.lastname: Li
authors.forename: David
authors.initials: D
authors.lastname: Carlsson
authors.forename: Chris
authors.initials: C
authors.lastname: Lohmann
authors.forename: Erik
authors.initials: E
authors.lastname: Suuronen
authors.forename: Sandy
authors.initials: S
authors.lastname: Vascotto
authors.forename: Karin
authors.initials: K
authors.lastname: Kobuch
authors.forename: Heather
authors.initials: H
authors.lastname: Sheardown
authors.forename: Rejean
authors.initials: R
authors.lastname: Munger
authors.forename: Masatsugu
authors.initials: M
authors.lastname: Nakamura
authors.forename: May
authors.initials: M
authors.lastname: Griffith
mesh_terms: D000818:Animals; D001672:Biocompatible Materials; D002642:Chick Embryo; D003094:Collagen; D003315:Cornea / Q000502:physiology*; D016039:Corneal Transplantation / Q000502:physiology*; D004847:Epithelial Cells / Q000502:physiology*; D005109:Extracellular Matrix / Q000502:physiology*; D005727:Ganglia, Spinal / Q000166:cytology / Q000196:embryology; D006801:Humans; D020100:Hydrogels; D015603:Keratinocytes / Q000166:cytology; D009416:Nerve Regeneration / Q000502:physiology*; D009842:Oligopeptides; D012038:Regeneration / Q000502:physiology*; D023822:Tissue Engineering / Q000379:methods
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D009842:Oligopeptides; C081571:tyrosyl-isoleucyl-glycyl-seryl-arginine; D003094:Collagen