Paclitaxel-eluting biodegradable synthetic vascular prostheses: a step towards reduction of neointima formation?
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.


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.
Innocente
Francesco
F
Departments of Cardiovascular Surgery, University Hospital of Geneva, Switzerland.
Mandracchia
Delia
D
Pektok
Erman
E
Nottelet
Benjamin
B
Tille
Jean-Christophe
JC
de Valence
Sarra
S
Faggian
Giuseppe
G
Mazzucco
Alessandro
A
Kalangos
Afksendiyos
A
Gurny
Robert
R
Moeller
Michael
M
Walpoth
Beat H
BH
D000818:Animals; D001696:Biomechanical Phenomena; D001807:Blood Vessel Prosthesis; D049109:Cell Proliferation / Q000187:drug effects; D006965:Hyperplasia; D008297:Male; D017239:Paclitaxel / Q000097:blood / Q000737:chemistry / Q000494:pharmacology*; D011091:Polyesters / Q000737:chemistry*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017539:Tunica Intima / Q000473:pathology*
D011091:Polyesters; C016240:polycaprolactone; D017239:Paclitaxel