This research plan builds upon the progress made with prior NIH funding but strikes out in a brand new direction. The next period of the research aims at harnessing the body's own healing capacity by creating cell-free synthetic grafts that can be rapidly remodeled by the host. The focus of the last funding period was cell-centered in vitro tissue engineering of arteries. The next stage of this project will completely bypass cell seeding and cell culture. We will use the cell-free polymer scaffolds directly as interposition grafts in abdominal aortas of mammalian hosts. The open porous graft will fully exploit the power of host remodeling more effectively than current vascular grafts that are dense and inhibit cell infiltration. The graft will function immediately as a non-thrombogenic conduit for blood flow in a similar fashion as a saphenous vein in coronary artery bypass surgery. We hypothesize that the extensive pores in the graft will facilitate host cell infiltration and the fast degrading polyer will enable rapid host remodeling to regenerate arteries in situ. This hypothesis is based on our strong preliminary data on rapid host cell infiltration and near complete regeneration of rat aorta 3 month post-implantation. The neo-arteries pulse synchronously with the host aorta and possess burst pressure and compliance comparable to native arteries. To our knowledge, this level of rapid host remodeling is unprecedented in reported vascular grafts.
Three specific aims will test this hypothesis in the next five years: 1. Study the relationship between the structure o the porous tube and host remodeling of the vascular grafts. 2. Determine the impact of mechanical properties of sheath material on the performance of the vascular graft in vivo. And 3. Investigate host remodeling of the vascular grafts at the cellular level. Success in cell-free tissue engineering will accelerate clinical translation and ultimately benefit patients suffering myocardial and peripheral ischemia. Insights gained from this research will lead to new approaches in regeneration of complex organs in the future.

Public Health Relevance

Vasculopathy and the subsequent ischemia are leading cause of mortality and disability in the United States and other industrialized countries. The ultimate goal of this project is to create biodegradable synthetic vascular grafts that will be remodeled by the host in situ to fully functional host arteries. This will provide a new approach to treat vasculopathy and ischemic diseases.

Agency
National Institute of Health (NIH)
Institute
National Heart, Lung, and Blood Institute (NHLBI)
Type
Research Project (R01)
Project #
2R01HL089658-05A1
Application #
8295168
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lundberg, Martha
Project Start
2007-07-25
Project End
2017-07-31
Budget Start
2012-08-01
Budget End
2013-07-31
Support Year
5
Fiscal Year
2012
Total Cost
$377,823
Indirect Cost
$130,070
Name
University of Pittsburgh
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
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Allen, Robert A; Wu, Wei; Yao, Mingyi et al. (2014) Nerve regeneration and elastin formation within poly(glycerol sebacate)-based synthetic arterial grafts one-year post-implantation in a rat model. Biomaterials 35:165-73
Lee, Kee-Won; Johnson, Noah R; Gao, Jin et al. (2013) Human progenitor cell recruitment via SDF-1? coacervate-laden PGS vascular grafts. Biomaterials 34:9877-85
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Lee, Kee-Won; Wang, Yadong (2011) Elastomeric PGS scaffolds in arterial tissue engineering. J Vis Exp :
Lee, Kee-Won; Stolz, Donna B; Wang, Yadong (2011) Substantial expression of mature elastin in arterial constructs. Proc Natl Acad Sci U S A 108:2705-10

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