While there are a number of surgical alternatives to autologous large diameter vascular grafts, i.e. allografts, xenografts, and synthetic vascular graft substitutes, there are no clinically acceptable alternatives to healthy autologous small diameter (<6mm) artery or vein. This lack of alternatives arises from luminal thrombosis and neointimal hyperplasia that occlude the substitute small diameter vessel. Growing a layer of intact endothelium in the lumen of small diameter vascular grafts represents a promising means of increasing graft patency. In this study we hypothesize that the clinical success of in vitro endothelialized small diameter ePTFE vascular grafts is dependent upon the confluence of three interacting factors: (1) the autologous sourcing of ECs, (2) the attachment, growth and retention of the layer of ECs to the graft lumen, and (3) the maintenance of an antithrombotic profile by the layer of ECs.
The specific aims of this competitive renewal are to (1) identify a reliable and viable source of blood-derived autologous EPCs isolated from the peripheral blood of adults with coronary artery disease, (2) transfect the EPCs with the gene for human thrombomodulin (hTM), (3) verify the adherence and expression of antithrombotic markers in native and hTM transfected EPCs seeded onto vascular graft surrogate films of Teflon AF, (4) verify adherence and expression of antithrombotic markers in native and hTM transfected EPCs sodded onto the lumen of 1 mm diameter ePTFE vascular grafts, and (5) test short term patency of ePTFE grafts sodded with native or hTM transfected EPC in nude rats. Human EPCs will be studied in anticipation of future clinical applications.

Public Health Relevance

While there are a number of surgical alternatives to autologous large diameter vascular grafts i.e. allografts, xenografts, and synthetic vascular graft substitutes, there are no clinically acceptable alternatives to healthy autologous small diameter (<6mm) artery or vein. We propose that growing a layer of intact, autologous endothelium in the lumen of small diameter ePTFE vascular grafts synthetic would provide a viable alternative for patients who lack suitable healthy autologous tissue.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
5R01HL044972-21
Application #
8270014
Study Section
Bioengineering, Technology and Surgical Sciences Study Section (BTSS)
Program Officer
Lee, Albert
Project Start
2009-05-01
Project End
2013-04-30
Budget Start
2012-05-01
Budget End
2013-04-30
Support Year
21
Fiscal Year
2012
Total Cost
$273,135
Indirect Cost
$98,218
Name
Duke University
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
044387793
City
Durham
State
NC
Country
United States
Zip Code
27705
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Reichert, William M (2013) Diversity and the Duke BME PhD program: then, now and moving forward. Ann Biomed Eng 41:2019-26
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Stroncek, John D; Grant, Bryan S; Brown, Melissa A et al. (2009) Comparison of endothelial cell phenotypic markers of late-outgrowth endothelial progenitor cells isolated from patients with coronary artery disease and healthy volunteers. Tissue Eng Part A 15:3473-86
Brown, Melissa A; Wallace, Charles S; Angelos, Mathew et al. (2009) Characterization of umbilical cord blood-derived late outgrowth endothelial progenitor cells exposed to laminar shear stress. Tissue Eng Part A 15:3575-87

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