Protesi vascolari sintetiche biodegradabili drug-eluting: modelli sperimentali in vitro ed in vivo

Small-calibre vascular prostheses (<6 mm) are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia. To overcome this we manufactured biodegradable small-calibre vascular prostheses using electrospun polycaprolactone (PCL)-based nanofibres with slow releasing paclitaxel (PTX), an anti-proliferative drug. PCL solution containing PTX (0-1% w:w) was used to prepare nonwoven nanofibre-based 2mm 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 up to 6 months. Patency, stenosis, tissue reaction and drug effect on endothelialisation, vascular remodelling and neo-intima formation (morphometry) were studied in vivo. In vitro: prostheses showed controlled morphology mimicking extracellular matrix (fibre diameter 500-2000nm) with mechanical properties similar to those of native vessels (tensile stress >1.4MPa, tensile strain >100%). Drug-loading had no negative impact on mechanical properties and drugs were released in a controlled manner over 1 month. In vivo: angiography showed 100% patency, no stenosis, no aneurysmal dilatation and there were no differences among the two groups. Major morphologic differences were found between the nondrug- loaded and drug-loaded prostheses. Endothelial coverage and cell ingrowth were significantly reduced and delayed in the PTX Group at 3 and 12 weeks but, neo-intima formation was significantly reduced in the drug-loaded grafts at 12 weeks. Degradable, electro-spun, nanofibre, polycaprolactone prostheses are promising since, in vitro they maintain their mechanical properties (regardless of drug-loading), and in vivo show good patency, reendothelialise and remodel with autologous cells. Drug loading delays endothelialisation and cellular ingrowth which may be problematic in degradable grafts. Conversely, it reduces neo-intima formation and thus may be an interesting option for small calibre vascular grafts. However, long-term follow-up studies are needed to confirm the usefulness of anti-proliferative drug-release in biodegradable scaffolds for cardiovascular clinical applications.