Novel strategies to improve the patency of vascular prostheses

Abstract

Two novel strategies to improve the patency of vascular prostheses are described in this thesis. To improve the outcome of synthetic vascular bypass surgery, cell seeding is a promising concept that has extensively been investigated and is still evolving. To improve the short term effects due to acute thrombotic occlusion, thrombogenicity of prosthetic material could be reduced by both 'endothelialization' of the graft or heparin bonding to the endoluminal surface. Both strategies potentially also reduce intimal hyperplasia (IH), as both endothelial cells and heparin are known to influence the process of IH development. Therefore, the emphases of the studies described were: 'auto-endothelialization' and 'thrombogenicity-reduction' of the vascular PTFE graft. The central questions of this thesis were: 1. Can auto-endothelialization of grafts be realised using anti-CD34 coating? 2. Does this coating reduce intimal hyperplasia? And 3. Does heparin immobilization reduce thrombogenicity of vascular grafts? 4. Is there a systemic effect of the locally immobilized heparin on the vascular grafts? To answer these questions in vitro, ex vivo and in vivo studies were performed, which are described in this thesis. Overall, we conclude that auto-endothelialization by antibody coating and heparin immobilization are techniques that have the potential to improve the patency of small diameter vascular grafts. From both the in vivo and in vitro anti-CD34 studies we conclude that the concept of auto-endothelialization can be realized by this coating technique. The 'perfect antibody' however, is not found yet, as a threefold increase of neo-intima formation was the result of the anti-CD34 coating and a-specific cells attached to the coated surface. From the ex vivo study we can conclude that heparin immobilization successfully reduces the thrombogenicity of ePTFE grafts. The major conclusion from the in vivo study, using the heparinized grafts is the lack of antibodies against the locally immobilized heparin, which is of great clinical importance. As stated earlier, the ideal conduit for (semi)acute vascular bypass procedures is the one that the surgeon can simply pick off the shelf, implant in the patient and which also resembles the patency of venous bypasses. At the time of writing, on the basis of the studies described in this thesis and the literature available, this specific heparinized graft seems to be the best choice. Of course, longer follow up studies are needed to delineate whether heparin immobilized prostheses truly perform as good as venous bypass grafts do. In theory, both reduction of thrombogenicity and reduction of IH might benefit this clinical dilemma.