Abstract 15315: Novel Drug Delivery Technology on Vascular Graft Implants Reduces Neointimal Hyperplasia in a Porcine Preclinical Model
Hundreds of implantable medical devices are made from the biologically inert material PTFE, and have been used in the medical industry since the 1950s. These devices may fail due to infection, inflammation, and thrombosis, and device failure often leads to reoperation, amputation, and death. Using ePTFE vascular grafts, rapamycin was embedded in a polymer coating over a 1 cm area at each end of the graft luminal surface. The coating technology involved drug incorporation into a proprietary methacrylate-based adhesive polymer. Monomer ratios used to generate the polymer were designed to provide a porous coating without compromising the flexibility or the intranodal spaces of the graft. Aortoiliac bypass grafting was performed in a porcine model using 6mm thin-walled ePTFE grafts. We previously demonstrated a 43% reduction in obstruction of the blood vessel after 4 weeks using the rapamycin coated graft (R-G) when compared to the industry standard uncoated graft (U-G). At sacrifice, animals with the R-G had longer explanted iliac anastomoses of 10.3 +0.26 mm vs. U-G (or polymer only coated (P-G)), 7.3 + 0.15 mm; P=0.0001). In addition to having longer anastomoses, the R-G recipients had less cross-sectional narrowing in the outflow graft (16.2% vs 28.5%; P = 0.0007) and decreased intimal thickness when indexed to U-G or P-G. Complete endothelial coverage of ePTFE was noted in all groups. Rapamycin levels were obtained from grafts, explanted arteries and blood samples at various time points after implantation. Despite being present in the arterial wall on post-operative day (POD) 28, rapamycin levels did not approach systemic toxicity. Rapamycin was not detectable in blood after POD 3. Based on attentuated total reflectance (ATR) and reflectance imaging (RI) studies, drug release was due primarily to diffusion through the surface polymer on the vascular graft and not by degradation or erosion of the coating. In conclusion, this novel drug-eluting technology has the potential to fundamentally alter the medical implant field as previously inert devices will serve as vehicles for local delivery of targeted therapeutics and may reduce mortality and morbidity, and impact health economics.
- © 2011 by American Heart Association, Inc.