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.
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.