MODIFICATION OF CORNEAL TISSUE ENGINEERED SCAFFOLDS TO PROMOTE EPITHELIALIZATION

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This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Attempts to augment and replace the cornea with synthetic materials have met with limited succeass, primarily because these devices have been unable to support and maintain a normal stratified epithelium. The fundamental problem is that the host epithelial cells recognize the polymer surface as other than stroma or "self" and, therefore, a degree of foreign body response is present throughout the life of the implant. Although natural materials often have good biocompatibility, they lack the strength to support tissue regeneration and the ability to withstand the natural wound remodeling process. It is advantageous, therefore, to consider combination strategies for leveraging the advantages of synthetic and natural materials for tissue engineering applications. For corneal material construction, a minimum 2-layer microstructured scaffold is specifically required to separate the epithelial layer from the stromal cell layer. The central part of the scaffold material must support infiltration and growth of stromal cells, whereas the outer surface of the scaffold must allow the adhesion and maintenance of the epithelial layer. Extracellular matrix proteins (ECMPs) and peptides covalently tethered to the scaffold surfaces are also needed to enhance cell growth. We propose to integrate novel chemistry, micro/nanofabrication, and cell biology methods to first understand and then control corneal both epithelial and stromal cell-material interactions as a method to engineer an effective corneal replacement/augmentation material. Our specific aims are as follows: Specific Aim I: To develop and characterize 3-dimensional scaffolds of silicone hydrogels, collagen, and chitosan (and/or copolymers thereof), as the framework for an optimal corneal replacement/augmentation material. Specific Aim II: To increase optimal cellular response to the developed polymer scaffold materials by modifying their surfaces with tethered ECMPs and peptides using novel micro/nanofabrication techniques. Specific Aim III: To quantify and analyze the cellular response to the developed polymer scaffolds using primary rabbit epithelial and keratocyte cell culture and corneal organ culture.