The control of endothelial motility on molecularly engineered surfaces may be an important step in the development of a biologically functional small diameter arterial prosthesis. We believe that mimicking features of cell contact mediated migration in self-assembling bioorganic films provides a rational design strategy for such an approach. Specifically, we intend to: (1) Synthesize and characterize composite lipid films as substrates for controlled endothelial migration. Integrin and glycosaminoglycan (GAG) binding oligopeptide ligands will be synthesized and used as pendant groups on phospholipid macromolecules. A GAG-lipid conjugate, based upon heparan sulphate, will also be synthesized as a molecular sink for basic Fibroblast Growth Factor (bFGF). Atomic level properties and film biostability characteristics will be investigated by vibrational spectroscopy and scanning probe microscopy. (2) Define the structural and chemical features of membrane-mimetic surfaces which modulate endothelial cell motility. Human endothelial cell adhesion and migration will be studied as a function of ligand type, density, and distribution. Likewise, the ability of bFGF, incorporated into supramolecular lipid assemblies, to enhance motility will be analyzed and related to its surface concentration and dissociation kinetics. (3) Characterize the biomimetic material properties which influence thromboresistance and spontaneous endothelialization in vivo. A self-expanding polymeric endovascular prosthesis, as a tool for initial in vivo investigations, will be fabricated, functionalized with a biomimetic film, and surface properties characterized. Acute platelet and fibrinogen deposition will be studied in a baboon ex vivo shunt model followed by characterizing endothelial responses in a limited series of primate implant studies.
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