The overall objective of this project is the production of biopolymeric materials suitable for use as a perforating keratoprosthesis. This device will consist of two components: (1) a central optical element that is transparent and supports epithelial adhesion and migration; and (2) a porous peripheral anchoring material that encourages fibroblast ingrowth, resulting in permanent wound apposition. The polymer comprising the central optical element will overlay the external surface of the peripheral anchoring material to ensure a continuous epithelial layer over the entire surface of the eye. The cell contacting surfaces of both polymers will be coated with proteins such as collagen, fibronectin or laminin, either singly or in combination to enhance cell proliferation and maintenance. Promising materials will be evaluated in vitro using the criteria established in preliminary experiments for predicting their capacity to support cell adhesion and growth in vitro and in vivo. Individual polymers as well as the composite keratoprosthesis will be evaluated in vivo in experimental animals for (a) the degree to which they induce corneal inflammation, (b) their ability to support the regeneration of surface epithelium and the ingrowth of fibroblasts peripherally, (c) their ability to resist enzymatic degradation, (d) their ability to resist the stresses to which they would be subjected in the anterior segment of the eye, and (e) their ability to remain transparent for an extended period while functioning as a full-thickness corneal replacement. The ability of biological adhesives, either alone or in conjunction with conventional suturing techniques, to secure the keratoprosthesis in vivo, will be evaluated. Achievement of our experimental goals will result in a prosthesis suitable for use as a full-thickness replacement of an opaque cornea. This would have considerable impact on the clinical treatment of corneal disease, the world's leading cause of blindness.
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