Regeneration of Corneal Cells and Nerves in an Implanted Collagen Corneal Substitute

• DOI: 10.1097/ico.0b013e3181658408
• Publication Date: 2008-05-22T07:10:23Z
• Authors: Christopher R McL...; Per Fagerholm; Lea Muzakare; Neil Lagali; John V Forrester; Lucia Kuffova; Mehrdad A Rafat; Yuwen Liu; Naoshi Shinozaki; Sandy G Vascotto; Rejean Munger; May Griffith
• Keywords: collagen; Swine; extracellular matrix; Biocompatible Materials; Ophthalmic Nerve; RE Ophthalmology; Collagen Type I; Cornea; Corneal Transplantation; Immunoenzyme Techniques; Prosthesis Implantation; Mice; 03 medical and health sciences; 0302 clinical medicine; cornea; grafts; Animals; Regeneration; nerve regeneration; membrane; biomechanical properties; mouse; porcine cornea; Mice, Inbred BALB C; model; Microscopy, Confocal; full-thickness; Epithelium, Corneal; Corneal Topography; Hydrogels; vivo confocal microscopy; matrix; Extracellular Matrix; Nerve Regeneration; RE; Artificial Organs; hydrogel; mechanical proper-ties; Biomarkers

Our objective was to evaluate promotion of tissue regeneration by extracellular matrix (ECM) mimics, by using corneal implantation as a model system.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.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.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.