The long-term objective of this work is the development of artificial extracellular matrix (aECM) proteins to be used in the fabrication of vascular grafts characterized by improving long-term patency. The approach is predicated on the following hypotheses: I). that existing synthetic vascular graft materials - specifically expanded polytetrafluoroethylene (ePTFE) and Dacron - are not optimal, either in terms of surface chemistry or with respect to mechanical properties, ii). that the mechanisms of healing of synthetic grafts are controlled at least in part by cellular interactions with the graft surface or with macromolecules, including plasma proteins or ECM proteins, deposited on that surface, iii). that a measure of control of cellular behavior at the graft surface can be gained by presentation of ligands for specific cell-surface receptors, and iv). that engineered variants of ECM proteins will allow control, both of the key mechanical properties of the graft, and of the presentation of ligands at the graft surface. The project will include: I). determination of endothelial cell spreading and adhesion behavior on crosslinked aECM proteins, ii). determination of the effect of aECM structure on endothelial cell migration and proliferation, and iii). in vitro analysis of inflammatory and thrombogenic responses to aECM proteins.
