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Neil S Lagali, Maria Xeroudaki, Muthukumar Thangavelu, Per Fagerholm, Anthony Mukwaya, Anton Lennikov, Mehrdad Rafat; Double-crosslinked bioengineered collagen implants for corneal stromal transplantation: evaluation in a porcine model. Invest. Ophthalmol. Vis. Sci. 2018;59(9):2251.
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© ARVO (1962-2015); The Authors (2016-present)
To develop and test a new bioengineered collagen scaffold as a replacement for donor corneal stromal tissue in transplantation surgery.
Medical-grade porcine skin type I collagen was crosslinked chemically and photochemically to form transparent hydrogels. Hydrogels were tested for mechanical strength, optical transmission, enzymatic degradation, biocompatibility, toxicity, and sterility. Cell compatibility was tested with human corneal epithelial cells in vitro, and in vivo biocompatibility was tested by subcutaneous implantation in rats for 8 weeks. Hydrogels formed into 7mm diameter curved corneal implants were evaluated by corneal transplantation in 10 minipigs for 6 months, using femtosecond laser-assisted lamellar or intrastromal keratoplasty models (5 minipigs each), with equal-sized autograft control groups. All procedures were performed with ethical approvals and followed the ARVO guidelines for use of animals in vision research.
Double-crosslinked hydrogels had greater mechanical strength relative to single-crosslinked versions, while transparency, resistance to degradation, biocompatibility, toxicity and sterility tests all exceeded threshold requirements for human use. Hydrogels supported epithelial cell growth and remained quiescent after 8 weeks of subcutaneous implantation. After intra-stromal transplantation, corneas with bioengineered implants or autografts replacing 250µm thickness of central stromal tissue were equally transparent with minimal thinning, fibrosis, or vascular ingrowth after 6 months. After anterior lamellar transplantation with overlying sutures, however, both bioengineered implants and autografts exhibited fibrosis, thinning, and vascularization. Intra-stromal transplantation preserved tissue structure, subbasal nerves, epithelial structure and keratocytes, while anterior lamellar implantation resulted in delayed nerve regeneration, disrupted stromal structure and myofibroblast invasion. All surgeries preserved native corneal endothelial cells.
Double-crosslinked bioengineered collagen implants have properties suitable for human corneal implantation and exhibit good biocompatibility with cells and tissues in vivo. Implantation intra-stromally yields results equivalent to native autografts while anterior lamellar keratoplasty gives sub-optimal outcomes due in part to sutures and limitations of the pig model.
This is an abstract that was submitted for the 2018 ARVO Annual Meeting, held in Honolulu, Hawaii, April 29 - May 3, 2018.
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