In vitro and in vivo evaluation of the BioStent

Abstract

The research on atherosclerosis therapy is ongoing for decades. This thesis is focused on lesions where interventional treatment is required, with special focus on stents. For care of late stage atherosclerosis two things are of high importance: first to exclude the diseased tissue and second to renew a healthy surface of endothelial cells. Nowadays, there is no treatment, except for vessel replacement, which guarantees those issues. Addressing those issues I hypothesize that a viable stent structure based on a tissue covered stent will prevent thrombocyte adhesion and hyperplasia.The aim of this study is to construct a tissue-covered endothelialized stent, the BioStent, and prove the hemocompatibility in vivo. Tissue engineering gives the chance to create new and healthy tissue which can replace the native one where it is damaged. By combining stents with tissue engineering, the stent is surrounded by autologous tissue and therefore on the one hand the foreign object reaction is avoided and on the other hand the damaged tissue is replaced by a new healthy tissue layer. The most important advantage is the endothelial layer with its known and important role of anti-thrombotic and anti-coagulative function, lining the lumen of the stent. For evaluation, different scaffolds (fibrin, elastin-like recombinamers), cell types (endothelial cells, endothelial progenitor cells) and stents (warp knitted, braided) were tested in vitro. For in vivo test, a warp knitted nitinol stent covered with fibrin-gel and EC was implanted in 5 sheep for 3 months. The stent structure was not strong enough to completely expand inside the vessel. Therefore the stents were implanted as interponate for in vivo evaluation. The precrimped BioStent proved to be implantable in carotid position over three months. Furthermore, the important crimping process could be performed without clinical relevant damage. The stent evidenced patency in four of five sheep over the planned implantation time of three months. The tissue analysis showed healthy tissue formation and a confluent endothelial layer orientated to the blood flow