Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes.
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.
Liu
Wenguang
W
Department of Cellular and Molecular Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Deng
Chao
C
McLaughlin
Christopher R
CR
Fagerholm
Per
P
Lagali
Neil S
NS
Heyne
Belinda
B
Scaiano
Juan C
JC
Watsky
Mitchell A
MA
Kato
Yasuhiro
Y
Munger
Rejean
R
Shinozaki
Naoshi
N
Li
Fengfu
F
Griffith
May
M
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
D001672:Biocompatible Materials; D024022:Fibrillar Collagens; D020100:Hydrogels; D010767:Phosphorylcholine; D003094:Collagen