Regeneration of corneal cells and nerves in an implanted collagen corneal substitute.
OBJECTIVE
Our objective was to evaluate promotion of tissue regeneration by extracellular matrix (ECM) mimics, by using corneal implantation as a model system.


METHODS
Carbodiimide cross-linked porcine type I collagen was molded into appropriate corneal dimensions to serve as substitutes for natural corneal ECM. These were implanted into corneas of mini-pigs after removal of the host tissue, and tracked over 12 months, by clinical examination, slit-lamp biomicroscopy, in vivo confocal microscopy, topography, and esthesiometry. Histopathology and tensile strength testing were performed at the end of 12 months. Other samples were biotin labeled and implanted into mice to evaluate matrix remodeling.


RESULTS
The implants promoted regeneration of corneal cells, nerves, and the tear film while retaining optical clarity. Mechanical testing data were consistent with stable, seamless host-graft integration in regenerated corneas, which were as robust as the untreated fellow corneas. Biotin conjugation is an effective method for tracking the implant within the host tissue.


CONCLUSIONS
We show that a simple ECM mimetic can promote regeneration of corneal cells and nerves. Gradual turnover of matrix material as part of the natural remodeling process allowed for stable integration with host tissue and restoration of mechanical properties of the organ. The simplicity in fabrication and shown functionality shows potential for ECM substitutes in future clinical applications.
University of Ottawa Eye Institute, Ottawa, Ontario, Canada.
Christopher R
CR
McLaughlin
Per
P
Fagerholm
Lea
L
Muzakare
Neil
N
Lagali
John V
JV
Forrester
Lucia
L
Kuffova
Mehrdad A
MA
Rafat
Yuwen
Y
Liu
Naoshi
N
Shinozaki
Sandy G
SG
Vascotto
Rejean
R
Munger
May
M
Griffith
D000818:Animals; D001187:Artificial Organs; D001672:Biocompatible Materials / Q000627:therapeutic use; D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000627:therapeutic use*; D003315:Cornea / Q000294:innervation*; D019781:Corneal Topography; D016039:Corneal Transplantation / Q000502:physiology*; D019573:Epithelium, Corneal / Q000166:cytology* / Q000378:metabolism; D005109:Extracellular Matrix; D020100:Hydrogels; D007124:Immunoenzyme Techniques; D051379:Mice; D008807:Mice, Inbred BALB C; D018613:Microscopy, Confocal; D009416:Nerve Regeneration / Q000502:physiology*; D009882:Ophthalmic Nerve / Q000502:physiology* / Q000648:ultrastructure; D019919:Prosthesis Implantation; D012038:Regeneration / Q000502:physiology; D013552:Swine; D013556:Swine, Miniature; D013718:Tensile Strength
D001672:Biocompatible Materials; D015415:Biomarkers; D024042:Collagen Type I; D020100:Hydrogels