Seeding of Titanium Surfaces and Nitinol Stents with Blood-Derived Endothelial Cells

Abstract

<p>Covering the metal surface of blood-contacting cardiovascular implants (stents, ventricular assist devices) with functional endothelium may reduce the incidence of clotting and restenosis complications and also reduce the need for risky anticoagulation therapy following implantation of such devices. We developed a novel cell therapy for seeding autologous endothelium onto blood-contacting vascular stents at the point of care to reduce thrombosis and stent restenosis. The proposed research tested the following hypotheses: (1) autologous endothelial cells (ECs) can spread on titanium (Ti) tubes and reduce thrombosis on the Ti surface <italic>in vivo</italic>; (2) shear stresses on the surfaces of an implanted carotid artery stent will be conducive to EC retention and function under arterial flow; and (3) nitinol stents seeded with ECs at the point of care will remain adherent and functional after stent deployment and arterial fluid shear stress conditions <italic>in vitro</italic> and <italic>in vivo</italic>. Based on the experiments reported herein, the primary conclusions of the dissertation are as follows: (1) autologous ECs significantly reduce thrombosis on Ti surfaces implanted into the bloodstream <italic>in vivo</italic>; (2) shear stresses on stent surfaces under carotid artery flow conditions are sufficiently low to be compatible with EC retention and function; (3) ECs seeded onto nitinol stents by infusion at the point of care are retained and spread to form a functional layer following deployment and arterial flow conditions both <italic>in vitro</italic> and <italic>in vivo</italic>.</p>