Cover Image

Collagen-Based Bioengineered Substitutes of Donor Corneal Allograft Implantation: Assessment and Hypotheses

Nataliya Pasyechnikova, Volodymyr Vit, Mykola Leus, Stanislav Iakymenko, Oleksiy Buznyk, Sergii Kolomiichuk, Illia Nasinnyk, Mohammad Mirazul Islam, May Griffith

Abstract


To fabricate donor corneal substitutes based on carbodiimide cross-linked porcine collagen, to study their in vitro and in vivo properties, and to elaborate new implantation techniques for the donor corneal collagen-based substitutes, this study had been performed. Bioengineered substitutes of corneal stroma (BSCS) were fabricated by cross-linking porcine type I collagen with 1-ethyl-3-(3-dimethyl aminopropyl) carbodiimide and N-hydroxysuccinimide, as previously described. Their refractive indices were measured using an Abbe refractometer. The mechanical properties were evaluated by their ability to tolerate interrupted stitches placed during deep lamellar keratoplasty performed on isolated rabbit eyes. BSCS were then implanted into one cornea of 8 rabbits and were followed-up for 12 months. Our BSCS had refractive indices of 1.24-1.3 (human cornea 1.37-1.38), and tolerated the placement of 12 interrupted stitches well. A new technique, the BSCS “stitchless” implantation, was developed. When implanted into rabbit corneas, BSCS remained stably integrated and clear during the 12 month follow-up. Non-intensive opacities within corneal layers (grade 1.5 on a scale of 0 to 4) were observed in 2/8 eyes during the 1st postoperative week, and in one eye the opacity resolved. In the 2nd eye a fine opacity (grade 1) remained. Light microscopy confirmed the integrity of the implants and the absence of inflammation in corneal stroma. The current data suggest that the BSCS fabricated in the Ukraine by cross-linking collagen is a good alternative to human donor corneas if medical grade porcine collagen is used. In addition, the new “stitchless” technique of BSCS implantation may decrease corneal substitute damage and accelerate its epithelialisation.


References


Whitcher JP, Srinivasan M, Upadhyay MP. Corneal blindness: a global perspective. Bull World Health Organ. 2001;79(3):214-21. PMID: 11285665.

Gilbert C, Foster A. Childhood blindness in the context of VISION 2020--the right to sight. Bull World Health Organ. 2001;79(3):227-32. PMID: 11285667.

Eye Bank Association of America, Eye banking statistical report. Washington, DC: Eye Bank Association of America; 1999.

Transplantologist Association of Ukraine, Annual Statistical Report. Kyiv: Transplantologist Association of Ukraine; 2011.

Iakymenko SA, Buznyk OI. Amniotic membrane transplantation in severe eye burns treatment. Oftalmol Zh. 2010;65(3):47-51.

Fernandes M, Sridhar MS, Sangwan VS, Rao GN. Amniotic membrane transplantation for ocular surface reconstruction. Cornea. 2005 Aug;24(6):643-53. PMID: 16015081.

Iakymenko SA. Retrospective analysis of keratoprosthesis development and results of application at the Filatov Institute during 40 years. Oftalmol Zh. 2006;61(6):63–70.

Chirila TV. An overview of the development of artificial corneas with porous skirts and the use of PHEMA for such an application. Biomaterials. 2001 Dec;22(24):3311-7. PMID: 11700803.

Liu Y, Gan L, Carlsson DJ, Fagerholm P, Lagali N, Watsky MA, Munger R, Hodge WG, Priest D, Griffith M. A simple, cross-linked collagen tissue substitute for corneal implantation. Invest Ophthalmol Vis Sci. 2006 May;47(5):1869-75. PMID: 16638993.

Merrett K, Fagerholm P, McLaughlin CR, Dravida S, Lagali N, Shinozaki N, Watsky MA, Munger R, Kato Y, Li F, Marmo CJ, Griffith M. Tissue-engineered recombinant human collagen-based corneal substitutes for implantation: performance of type I versus type III collagen. Invest Ophthalmol Vis Sci. 2008 Sep;49(9):3887-94. PMID: 18515574.

Fagerholm P, Lagali NS, Merrett K, Jackson WB, Munger R, Liu Y, Polarek JW, Söderqvist M, Griffith M. A biosynthetic alternative to human donor tissue for inducing corneal regeneration: 24-month follow-up of a phase 1 clinical study. Sci Transl Med. 2010 Aug 25;2(46):46ra61. PMID: 20739681.

Liu W, Deng C, McLaughlin CR, Fagerholm P, Lagali NS, Heyne B, Scaiano JC, Watsky MA, Kato Y, Munger R, Shinozaki N, Li F, Griffith M. Collagen-phosphorylcholine interpenetrating network hydrogels as corneal substitutes. Biomaterials. 2009 Mar;30(8):1551-9. PMID: 19097643.

McLaughlin CR, Acosta MC, Luna C, Liu W, Belmonte C, Griffith M, Gallar J. Regeneration of functional nerves within full thickness collagen-phosphorylcholine corneal substitute implants in guinea pigs. Biomaterials. 2010 Apr;31(10):2770-8. PMID: 20042235.

Liu L, Kuffová L, Griffith M, Dang Z, Muckersie E, Liu Y, McLaughlin CR, Forrester JV. Immunological responses in mice to full-thickness corneal grafts engineered from porcine collagen. Biomaterials. 2007 Sep;28(26):3807-14. PMID: 17537502.


Full Text: Full text PDF

Creative Commons License
This work is licensed under a Creative Commons Attribution 3.0 License.