Basement membrane features that greatly influence cell function include compliance, specific proteins and functional groups, a reservoir of growth factor and other trophic agents, and a complex three-dimensional topography into which adherent cells extend processes, and formadhesion plaques. Thre three-dimensional submicron and nanoscale topography of the underlying substrate, and substrate compliance, independent of specific receptor-ligand interactions has been recently shown to influence fundamental cell behaviors. This proposal focuses on the interactions of corneal epithelial cells with biomimetic materials designed for integration into an implantable device. Our design parameters will be based on the premise that mimicking the structure, chemistry and compliance of the native basement membrane will be conducive to resurfacing and maintenance of a fully differentiated and functional epithelium by host cells. The overall purpose of this proposal is to determine the interaction of compliance, surface chemistry via adhesive peptide ligands, and topography mimicking features of the basement membrane underlying the corneal epithelium to determine design parameters for improved tissue architecture and function, and for integration into the design and fabrication of keratoprostheses. In this application, a multi-disciplinary approach is proposed to test 3 hyphothese using quantitative morphologic techniques, in vitro methodologies in cell biology, molecular biology and state-of-the-art nanoscale fabrication techniques. Hypothesis 1: Combined micro, submicron, and nanoscale topography and compliance will differentially affect cell attachment and spreading, proliferation, and migration. Hypothesis 2: Combining homogeneous and heterogeneous presentations of peptide sequences and topography will synergistically impact cell proliferation, adhesion and migration. Hypothesis 3: Combining biomimetic topography, compliance and surface chemistry will allow for the determination of materials parameters to enhance or retard cell behaviors within well-defined areas for integration into novel corneal equivalents.
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