Controlled Release Vascular Grafts

Project: Research project

Project Details

Description

DESCRIPTION (provided by applicant): In the United States, it is estimated that 8 million people suffer from peripheral artery disease (PAD). PAD is characterized by a gradual reduction in blood flow to the muscular arteries of the lower extremities caused by atherosclerosis. For those with severe PAD, lower extremity bypass grafting remains the predominant option for limb salvage. Although native vessels remain the gold standard conduit for bypass grafting, they are not available in approximately one-third of patients due to intrinsic venous disease or prior vein harvesting. In these cases, expanded polytetrafluoroethylene (ePTFE) grafts are the most commonly used alternative despite dismal patency rates due to the formation of thrombosis and neointimal hyperplasia. To address these problems, many researchers have been investigating alternative strategies that involve surface modification of the graft's lumen. However, approaches to date have met with limited success. Poly(1,8 octanediol citrate) (POC)-coated ePTFE grafts offer a potential alternative as they have been shown to be biocompatible, compliant, and have anti-thrombogenic properties in vitro and in vivo in a porcine animal model. Furthermore, POC can serve as a vehicle for the controlled release of drugs. A potential drug candidate, all-trans retinoic acid (ATRA), has been shown to inhibit smooth muscle cell proliferation and neointimal hyperplasia in several animal models as well as induce antithrombotic genes and upregulate nitric oxide in vascular endothelial cells. The objective of this proposal is to develop a biocompatible, non- thrombogenic POC-ePTFE vascular graft that can release, in a controlled manner, ATRA and assess whether the controlled release of this small molecule can reduce neointimal hyperplasia and thrombosis. Toward this goal, the specific aims are to a) fabricate non-thrombogenic ATRA-eluting POC-ePTFE grafts with varying release rates and b) assess the effect of the controlled rel
StatusFinished
Effective start/end date9/10/098/31/11

Funding

  • VesselTek BioMedical LLC (Agmt 05-12-10 // 1R43HL096217-01A1)
  • National Heart, Lung, and Blood Institute (Agmt 05-12-10 // 1R43HL096217-01A1)

Fingerprint

Explore the research topics touched on by this project. These labels are generated based on the underlying awards/grants. Together they form a unique fingerprint.