Blockage of blood vessels due to atherosclerosis is one of the main causes of mortality and morbidity in the United States resulting in 600,000 blood vessel replacement or revascularization procedures each year at a cost of over 1 billion dollars. Unfortunately, autologous grafts are often not an option for as many as one third of patients and synthetic grafts used to replace small-diameter blood vessels have high rates of failure due to thrombosis and neointimal hyperplasia. This proposal will investigate a bioengineering approach to improve the function and safety of synthetic grafts, specifically expanded polytetrafluoroethylene (ePTFE). The overall goal of this proposal is to evaluate whether an endothelial progenitor cells (EPC)-derived bioengineered ePTFE graft is feasible for patients with confirmed peripheral arterial disease (PAD) and to investigate the safety and efficacy of bioengineered grafts in a large animal model. In particular, we will investigate the use of pioglitazone, a peroxisome proliferator-activated receptor ? (PPAR-?) agonist, as a novel strategy to increase EPC colony formation and cell proliferation as patients with PAD have been reported to have reduced EPC numbers with impaired function. During the pre-clinical trials of this proposal we will develop cell isolation and cell-seeding protocols that can be readily adapted for use in the hospital setting.
The specific aims are to: 1. assess whether circulating EPCs from patients with PAD are a viable cell source for a cell-based bioengineered vascular graft, and 2. evaluate the safety and efficacy of the bioengineered ePTFE grafts in an atherosclerotic swine carotid artery ePTFE bypass model. Given the widespread nature of atherosclerosis and peripheral artery disease, the innovative approach taken in this proposal is expected to directly improve patient care of millions of Americans. This proposal will allow us to gather the necessary expertise and data to design a clinical trial to assess early stage efficacy of the bioengineered grafts.

Public Health Relevance

Blockage of blood vessels due to atherosclerosis is one of the main causes of mortality and morbidity in the United States resulting in 600,000 blood vessel replacement or revascularization procedures each year at a cost of over 1 billion dollars. This proposal will combine advances in progenitor cell research and biomaterial design to improve the function and safety of synthetic grafts, specifically expanded polytetrafluoroethylene (ePTFE). During the pre-clinical trials of this proposal we will develop cell isolation and cell-seeding protocols that can be readily adapted for use in the hospital setting.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Research Project (R01)
Project #
1R01EB017129-01A1
Application #
8578623
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Hunziker, Rosemarie
Project Start
2013-08-15
Project End
2017-07-31
Budget Start
2013-08-15
Budget End
2014-07-31
Support Year
1
Fiscal Year
2013
Total Cost
$437,589
Indirect Cost
$154,360
Name
Northwestern University at Chicago
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
van Lith, Robert; Gregory, Elaine K; Yang, Jian et al. (2014) Engineering biodegradable polyester elastomers with antioxidant properties to attenuate oxidative stress in tissues. Biomaterials 35:8113-22
Yang, Jian; van Lith, Robert; Baler, Kevin et al. (2014) A thermoresponsive biodegradable polymer with intrinsic antioxidant properties. Biomacromolecules 15:3942-52