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(Circulation. 2009;120:S37-S45.)
© 2009 American Heart Association, Inc.

Myocardial Protection, Perioperative Management, and Vascular Biology

Paclitaxel-Eluting Biodegradable Synthetic Vascular Prostheses

A Step Towards Reduction of Neointima Formation?

Francesco Innocente, MD; Delia Mandracchia, PhD; Erman Pektok, MD; Benjamin Nottelet, PhD; Jean-Christophe Tille, MD, PhD; Sarra de Valence, MSc; Giuseppe Faggian, MD; Alessandro Mazzucco, MD; Afksendiyos Kalangos, MD, PhD, FECTS; Robert Gurny, PhD; Michael Moeller, PhD; Beat H. Walpoth, MD, FAHA

From the Departments of Cardiovascular Surgery (F.I., E.P., A.K., B.H.W.) and Clinical Pathology (J.-C.T.), University Hospital of Geneva, Faculty of Medicine, Switzerland; the Department of Cardiovascular Surgery (F.I., G.F., A.M.), University of Verona Medical School, Italy; the Department of Cardiac Surgery (F.I.), IRCCS Policlinico San Donato, Milan, Italy; the School of Pharmaceutical Sciences (D.M., B.N., S.d.V., R.G., M.M.), University of Geneva, University of Lausanne, Switzerland; and the Department of Cardiovascular Surgery (E.P.), Yeditepe University, Istanbul, Turkey.

Correspondence to Beat H. Walpoth, MD, FAHA, Director, Cardiovascular Research, Clinical and Experimental, Service of Cardiovascular Surgery, University Hospital, 4 rue Gabrielle-Perret-Gentil, 1211 Geneva 14, Switzerland. E-mail beat.walpoth{at}hcuge.ch

Background— Clinical small-caliber vascular prostheses are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia. We thus prepared biodegradable small-caliber vascular prostheses using electrospun polycaprolactone (PCL) with slow-releasing paclitaxel (PTX), an antiproliferative drug.

Methods and Results— PCL solutions containing PTX were used to prepare nonwoven nanofibre-based 2-mm ID prostheses. Mechanical morphological properties and drug loading, distribution, and release were studied in vitro. Infrarenal abdominal aortic replacement was carried out with nondrug-loaded and drug-loaded prostheses in 18 rats and followed for 6 months. Patency, stenosis, tissue reaction, and drug effect on endothelialization, vascular remodeling, and neointima formation were studied in vivo. In vitro prostheses showed controlled morphology mimicking extracellular matrix with mechanical properties similar to those of native vessels. PTX-loaded grafts with suitable mechanical properties and controlled drug-release were obtained by factorial design. In vivo, both groups showed 100% patency, no stenosis, and no aneurysmal dilatation. Endothelial coverage and cell ingrowth were significantly reduced at 3 weeks and delayed at 12 and 24 weeks in PTX grafts, but as envisioned, neointima formation was significantly reduced in these grafts at 12 weeks and delayed at 6 months.

Conclusions— Biodegradable, electrospun, nanofibre, polycaprolactone prostheses are promising because in vitro they maintain their mechanical properties (regardless of PTX loading), and in vivo show good patency, reendothelialize, and remodel with autologous cells. PTX loading delays endothelialization and cellular ingrowth. Conversely, it reduces neointima formation until the end point of our study and thus may be an interesting option for small caliber vascular grafts.

Key Words: coronary disease • endothelium • intimal hyperplasia • paclitaxel elution • vascular prostheses