title: Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes.
abstract: A biointeractive collagen-phospholipid corneal substitute was fabricated from interpenetrating polymeric networks comprising 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide and N-hydroxysuccinimide crosslinked porcine atelocollagen, and poly(ethylene glycol) diacrylate crosslinked 2-methacryloyloxyethyl phosphorylcholine (MPC). The resulting hydrogels showed an overall increase in mechanical strength beyond that of either original component and enhanced stability against enzymatic digestion (by collagenase) or UV degradation. More strikingly, these hydrogels retained the full biointeractive, cell friendly properties of collagen in promoting corneal cell and nerve in-growth and regeneration (despite MPC's known anti-adhesive properties). Measurements of refractive indices, white light transmission and backscatter showed the optical properties of collagen-MPC are comparable or superior to those of the human cornea. In addition, the glucose and albumin permeability were comparable to those of human corneas. Twelve-month post-implantation results of collagen-MPC hydrogels into mini-pigs showed regeneration of corneal tissue (epithelium, stroma) as well as the tear film and sensory nerves. We also show that porcine collagen can be substituted with recombinant human collagen, resulting in a fully-synthetic implant that is free from the potential risks of disease transmission (e.g. prions) present in animal source materials.
authors.affiliation: Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Liu
authors.forename: Chao
authors.initials: C
authors.lastname: Deng
authors.forename: Christopher R
authors.initials: CR
authors.lastname: McLaughlin
authors.forename: Per
authors.initials: P
authors.lastname: Fagerholm
authors.forename: Neil S
authors.initials: NS
authors.lastname: Lagali
authors.forename: Belinda
authors.initials: B
authors.lastname: Heyne
authors.forename: Juan C
authors.initials: JC
authors.lastname: Scaiano
authors.forename: Mitchell A
authors.initials: MA
authors.lastname: Watsky
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Kato
authors.forename: Rejean
authors.initials: R
authors.lastname: Munger
authors.forename: Naoshi
authors.initials: N
authors.lastname: Shinozaki
authors.forename: Fengfu
authors.initials: F
authors.lastname: Li
authors.forename: May
authors.initials: M
authors.lastname: Griffith
mesh_terms: D000818:Animals; D001672:Biocompatible Materials / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism*; D003315:Cornea / Q000378:metabolism* / Q000473:pathology / Q000528:radiation effects / Q000648:ultrastructure; D024022:Fibrillar Collagens / Q000648:ultrastructure; D005612:Freeze Drying; D006801:Humans; D020100:Hydrogels / Q000378:metabolism*; D009682:Magnetic Resonance Spectroscopy; D008422:Materials Testing; D019563:Mechanics; D018613:Microscopy, Confocal; D010767:Phosphorylcholine / Q000378:metabolism*; D019919:Prosthesis Implantation; D011817:Rabbits; D013057:Spectrum Analysis; D017154:Stromal Cells / Q000528:radiation effects / Q000648:ultrastructure; D034421:Sus scrofa; D014466:Ultraviolet Rays
chemical_list: D001672:Biocompatible Materials; D024022:Fibrillar Collagens; D020100:Hydrogels; D010767:Phosphorylcholine; D003094:Collagen