Performance of a polyurethane vascular prosthesis carrying a dipyridamole (Persantin) coating on its lumenal surface Yvette B. J. Aldenhoff, 1 Frederik H. van der Veen, 2 Joost ter Woorst, 3 Jo Habets, 2 Laura A. Poole–Warren, 4 Leo H. Koole 1 1 Center for Biomaterials Research, University of Maastricht, P.O. Box 616, 6200 MD Maastricht, The Netherlands 2 Department of Cardiothoracic Surgery, Academic Hospital Maastricht, Maastricht, The Netherlands 3 Department of Cardiopulmonary Surgery, Catharina Hospital, Eindhoven, The Netherlands 4 Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia Received 6 December 1999; accepted 25 July 2000 Abstract: A porous polyurethane vascular prosthesis with an internal diameter of 5 mm was studied. The graft carries a coating of immobilized dipyridamole (Persantin) on the surface of its lumen. Dipyridamole is a potent nontoxic in- hibitor of platelet activation/aggregation, and also a strong inhibitor of vascular smooth muscle cell proliferation. The polyurethane material is also known as Chronoflex, and already finds use as a vascular access graft. The coated vas- cular graft was studied in vitro (hemocompatibility, interac- tion with blood platelets and cultured endothelial cells), as well as in two established in vivo models. In the first in vivo study, coated grafts were implanted in goats, as a bypass of the carotid artery (four animals, eight grafts, length of the graft was approximately 12 cm). Four uncoated grafts were used as controls in otherwise identical experiments. In the second in vivo experiment, eight sheep were used. Each ani- mal received one coated and one uncoated prosthesis as an interposition graft in the carotid artery (length of the graft was 4 cm). The in vitro experiments revealed that the dipy- ridamole coating has three beneficial effects: reduced throm- bogenicity, reduced adherence of blood platelets, and ac- commodation of a confluent monolayer of endothelial cells. The goat experiments showed patency of the coated grafts in three of the eight cases. The sheep experiments were not useful for the evaluation of the dipyridamole coating be- cause deterioration of the polyurethane material was ob- served. The in vivo results indicate that the dipyridamole coating may positively influence the patency rate, probably because the coating promotes the growth of an endothelial cell lining. The sheep data show, however, that the limited stability of the Chronoflex material precludes its issue for the construction of permanent small-bore vascular grafts. © 2000 John Wiley & Sons, Inc. J Biomed Mater Res 54: 224– 233, 2001 Key words: vascular prosthesis; polyurethane; dipyrid- amole; endothelial cells INTRODUCTION Clinical application of synthetic small-bore arterial prostheses [internal diameter (i.d.) <6 mm] continues to meet with substantial difficulties. 1 The primary fail- ure modes are thrombus formation in the short term, and intimal hyperplasia (particularly at the anastomo- ses) in the longer term. Synthetic vascular prostheses are used primarily to substitute rather large peripheral blood vessels. In more critical situations, such as in aortocoronary bypass surgery, autologous grafts (par- ticularly the internal mammary artery and the saphe- nous vein) are clearly superior to their synthetic coun- terparts. We are, however, faced with a growing number of patients who lack satisfactory autologous conduit, be- cause of prior removal, disease, or inadequate size. It is for this reason that the search for a truly functional small-bore vascular prosthesis is an active area of re- search and development. This has led to several inter- esting approaches: 1. seeding of the lumen of an elastic and compliant polymeric tube with autologous endothelial cells; 2,3 2. application of a hemocompatible coating on the lumen, e.g., through immobilization of heparin; 4 3. coating of the lumen with a biocompatible and biodegradable substance, such as collagen, 5 albu- min, 6 or poly(ethyleneglycol)/poly(lactic acid) block copolymer. 7,8 Such a coating provides a he- Correspondence to: L. H. Koole; e-mail: l.koole@bioch. unimaas.nl Contract grant sponsor: EUREKA program (via the Dutch Ministry of Economic Affairs) © 2000 John Wiley & Sons, Inc.