Abstract 5859: Drug Eluting Degradable Synthetic Vascular Prosthesis: A Step Towards Shelf-ready Coronary Artery Bypass Grafts
OBJECTIVES: Small-calibre vascular prostheses (<6mm) are unsatisfactory. Reasons for failure are early thrombosis and late intimal hyperplasia/infection. To overcome this we manufactured biodegradable small-calibre vascular prosthesis using electrospun polycaprolactone (PCL)-based nanofibres with slow releasing anti-inflammatory or anti-proliferative drugs.
METHODS: PCL solution containing Dexamethasone or Paclitaxel (0–10% w:w) was used to prepare non-woven nanofibre-based 2mm ID prostheses. Mechanical, morphological properties and drug release were studied in vitro. Patency, degradation, tissue reaction and drug effect (morphology) were studied in vivo. Infrarenal abdominal aortic replacement was carried out with non-drug-loaded and drug-loaded prostheses in 45 rats and followed up to 6 months.
RESULTS: In vitro prostheses showed controlled morphology mimicking extra-cellular 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 no difference in patency among the non-drug-loaded and drug-loaded prostheses (94%) and no aneurysmal dilatation was found. Major morphologic differences were found between the non-drug-loaded and drug-loaded prostheses, e.g. minimal inflammation in Dexamethasone-eluting grafts and minimal cell ingrowth in Paclitaxel-eluting grafts.
CONCLUSIONS: 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, re-endothelialise and remodel with autologous cells. Drug-loading induces less inflammation and tissue reaction and thus is a promising alternative as shelf-ready coronary bypass grafts, but long-term follow-up studies are needed to confirm the usefulness of drug-releasing, biodegradable scaffolds for cardiovascular clinical applications.