Designing contact lenses for epithelial cell transfer: effect of surface geometry, surface coating and cell motility

Abstract

Corneal wound healing is a complex, and highly coordinated process of cell-cell signaling, cell spreading, migration, proliferation, and cell-extracellular matrix interaction. The main limitation in natural wound healing is that cells can only fill in the wound void from the outside wound margin. We hypothesize that epithelial cells applied to the interior of a wound will attach to the exposed extracellular matrix of the wound, and accelerate the healing process. In order to deliver epithelial cells to wounds, we have developed a cell transfer contact lens. Our objective was to produce and evaluate transfer contact lens designs that allow for primary epithelial cell attachment and in vitro culture growth, and in addition after application result in the transfer of a portion of these cells to wound areas to aid in re-epithelialization of corneal injuries. In the process of meeting these design criteria, we explored the use of surface topographies and surface coatings to enhance cell transfer. We found that cell transfer from Polydimethylsiloxane contact lenses to extracellular matrix was a function of both cell motility and adhesion. In order to enhance cell transfer through the modulation cell motility and adhesion, we explored some of the underlying biological mechanisms of these two inter-related cellular behaviors. Though there were many potential molecular targets to augment cellular adhesion and motility, we specifically explored the regulation of cell-cell contacts, which have a profound impact on cell phenotype and migration. Normal corneal epithelial cells are motile cells that move slowly as a sheet. In contrast, fibroblasts move more quickly as individual cells. When epithelial cells exist as individual cells at very low cell density, they are more motile and more closely resemble fibroblast cells. Individual epithelial cells do not exhibit cell junction proteins. In this investigation we altered Bves, a protein we have shown is associated with tight junctions, in an effort to make epithelial cells become more like fibroblasts regardless of cell density. This transition from an epithelial cell type to a fibroblastic cell type is called epithelial-mesenchymal transition, and has broad reaching implications for other fields such as metastasis in cancer biology.