Date of Award
Master of Science (MS)
Webb , Ken
Ramamurthi , Anand
Cardiovascular diseases are the leading cause of death worldwide as reported by the World Health Organization. Biomaterials have been extensively used in blood-contacting applications as heart valves, stents, grafts and catheters. However failure due to thrombosis hinders the long term patency and potential of these devices. Purified elastin scaffolds derived from porcine arteries as potential vascular graft materials are being investigated in our laboratory. In this study, we investigated the influence of factors such as shear stress and the presence of plasma proteins on the platelet response, and endothelial cell retention on purified elastin scaffolds to evaluate their hemocompatibility.
Elastin scaffolds showed minimal platelet attachment and activation as compared to collagen scaffolds under physiologically relevant conditions - in the presence of shear and plasma proteins. Also, the absence of plasma proteins significantly augmented the platelet response to the underlying substrate, especially under shear. Contribution of fibrinogen adsorption towards platelet attachment was studied by Circular Dichroism. Although a higher amount of fibrinogen was adsorbed on elastin surfaces than collagen, the conformation of adsorbed protein was similar to native fibrinogen on both collagen and elastin surfaces. Therefore, with our testing conditions, the role of fibrinogen in contributing to the difference in platelet activity on these two scaffolds was not apparent. Plasma recalcification time reasserted thromboresistance of elastin scaffolds showing more than a two fold increase in clotting time as compared to collagen.
The purified elastin scaffolds showed good retention of endothelial cells in static cultures but when cells were plated under shear significantly lower number of cells were able to attach to elastin surfaces. Role of integrins in endothelial cell adhesion was studied by adhesion inhibition assays. Both αv and β1 receptor subunits exhibited a significant contribution to the endothelial adhesion process to elastin scaffolds as blocking these receptors by their respective antibodies significantly lowered the number of cells attached to elastin under static conditions.
Further studies are needed to delineate the effects of the adsorption of other plasma proteins such as vWF on elastin hemocompatibility. Our current studies indicate that endothelialization of elastin scaffolds could be improved by activating specific integrin receptors on the cells thereby promoting their interaction with the substrate. Overall, purified elastin scaffolds displayed superior hemocompatibility than collagen scaffolds and with better endothelialization could become potential candidates for vascular replacement.
Swaminathan, Nithya, "HEMOCOMPATIBILITY AND ENDOTHELIALIZATION OF ELASTIN AND COLLAGEN SCAFFOLDS: THE ROLE OF PLASMA PROTEINS, SHEAR STRESS AND INTEGRINS" (2010). All Theses. 903.