title: Innervation of tissue-engineered recombinant human collagen-based corneal substitutes: a comparative in vivo confocal microscopy study.
abstract: OBJECTIVE
  To compare reinnervation in recombinant human collagen-based corneal substitutes with allografts during a 1-year postimplantation follow-up period in pigs. A retrospective comparison to innervation in porcine collagen-based biosynthetic grafts was also performed.
  
  
  METHODS
  Pigs received a corneal allograft or a substitute made of either recombinant human type-I or -III collagen. In vivo confocal microscopic examination of the central cornea of surgical and untouched control eyes before surgery and at 2, 6, and 12 months after surgery was performed to quantify the number, density, and diameter of nerves at various corneal depths.
  
  
  RESULTS
  By 12 months after surgery, the number and density of regenerated nerves in the anterior and deep anterior corneal stroma recovered to preoperative and control levels in both types of substitute grafts and in the allografts. In the subepithelial and subbasal regions, however, significantly fewer nerves were detected relative to those in control subjects at 12 months, regardless of graft type (P < 0.05), similar to the behavior of porcine collagen-based biosynthetic grafts. An absence of thick stromal nerve trunks (diameter, >10 mum) in all grafts, irrespective of material type, indicated that nerve regeneration in grafts was accompanied by persistent morphologic changes.
  
  
  CONCLUSIONS
  Nerve regeneration in recombinant human collagen-based biosynthetic corneal grafts proceeded similarly to that in allograft tissue, demonstrating the suitability of recombinant human collagen constructs as nerve-friendly corneal substitutes. Furthermore, only minor differences were noted between type-I and -III collagen grafts, indicating an insensitivity of nerve regeneration to initial collagen type.
authors.affiliation: University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
authors.forename: Neil
authors.initials: N
authors.lastname: Lagali
authors.forename: May
authors.initials: M
authors.lastname: Griffith
authors.forename: Per
authors.initials: P
authors.lastname: Fagerholm
authors.forename: Kimberley
authors.initials: K
authors.lastname: Merrett
authors.forename: Melissa
authors.initials: M
authors.lastname: Huynh
authors.forename: Rejean
authors.initials: R
authors.lastname: Munger
mesh_terms: D000818:Animals; D001187:Artificial Organs / Q000592:standards*; D003094:Collagen / Q000235:genetics*; D003315:Cornea / Q000166:cytology* / Q000502:physiology*; D016039:Corneal Transplantation / Q000379:methods; D006801:Humans; D018613:Microscopy, Confocal; D009416:Nerve Regeneration / Q000502:physiology; D009900:Optic Nerve / Q000502:physiology; D011994:Recombinant Proteins / Q000378:metabolism; D013552:Swine; D023822:Tissue Engineering / Q000379:methods*; D014183:Transplantation, Heterologous; D014184:Transplantation, Homologous
chemical_list: D011994:Recombinant Proteins; D003094:Collagen