Title: Endothelialization of Vascular Biomaterials
In developing blood-contacting vascular biomaterials, a confluent endothelial cell (EC) monolayer may be required to avoid adverse blood reactions. In vitro, the hemostatic properties (“thrombogenicity”) of ECs have typically been char-acterized using anticoagulated blood, static or non-physiologic flow conditions, and short blood exposure times. Con-sequently, the relevance of these findings for in vivo applications remains uncertain. Moreover, there have been few studies of the reactivity of EC constructs in vivo, and no studies have been reported that systematically relate the in vitro properties of endothelialized surfaces with their responses in vivo. Accordingly, it is now recognized within the tissue engineering community that a key impediment to further progress towards applications in man is the lack of predictive animal models that will enable the rational design of cellular constructs. We are characterizing the in vitro and ex vivo pro-hemostatic and anti-hemostatic properties of ECs (that can affect platelets and coagulation), and im-portant in vivo responses of thrombosis and vascular healing in a physically relevant primate model. Endothelial out-growth cells (EOCs), isolated from the circulating endothelial progenitor cells of baboons, have been seeded on pro-tein-coated ePTFE vascular grafts. We have studied the role of extracellular matrix coatings and hemodynamic pre-conditioning on the EOC phenotype, particularly related to coagulation and inflammation. Subsequently, in an ex vivo baboon shunt model, platelet and fibrin accumulation were measured under conditions of controlled, native blood flow. Finally, the endothelialized vascular grafts were implanted as aorto-iliac interposition grafts for 28 days. After a thorough evaluation of potential correlations, a linear regression model using in vitro data was established to predict platelet accumulation. This regression correlated significantly and strongly to both ex vivo platelet and in vivo intimal hyperplasia data. This is the first work of this type—attempting to determine predictors for vascular graft performance from in vitro endothelial markers, and while future work should examine the scope of the model by applying it to other endothelialized grafts, we are encouraged by these results, which may aid in improving translation of small diameter vascular grafts into clinical improvements.
This seminar is partially funded by the Visiting Women & Minority Lecturer/Scholar Series which is funded by the President’s Office and a grant to the Office of Institutional equity from the State of Michigan’s King-Chavez-Parks Initiative