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 #
5R01HL089658-06
Application #
8519515
Study Section
Biomaterials and Biointerfaces Study Section (BMBI)
Program Officer
Lundberg, Martha
Project Start
2007-07-25
Project End
2017-07-31
Budget Start
2013-08-01
Budget End
2014-07-31
Support Year
6
Fiscal Year
2013
Total Cost
$350,726
Indirect Cost
$120,930
Name
University of Pittsburgh
Department
Biomedical Engineering
Type
Schools of Engineering
DUNS #
004514360
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
Lee, Soo Hyon; Lee, Kee-Won; Gade, Piyusha S et al. (2018) Microwave-assisted facile fabrication of porous poly (glycerol sebacate) scaffolds. J Biomater Sci Polym Ed 29:907-916
Ding, Xiaochu; Wu, Yen-Lin; Gao, Jin et al. (2017) Tyramine functionalization of poly(glycerol sebacate) increases the elasticity of the polymer. J Mater Chem B 5:6097-6109
Procter, Nathan Ek; Ball, Jocasta; Ngo, Doan Tm et al. (2016) Gender and tachycardia: independent modulation of platelet reactivity in patients with atrial fibrillation. J Geriatr Cardiol 13:202-8
Khosravi, Ramak; Best, Cameron A; Allen, Robert A et al. (2016) Long-Term Functional Efficacy of a Novel Electrospun Poly(Glycerol Sebacate)-Based Arterial Graft in Mice. Ann Biomed Eng 44:2402-16
Johnson, Noah R; Wang, Yadong (2015) Coacervate delivery of HB-EGF accelerates healing of type 2 diabetic wounds. Wound Repair Regen 23:591-600
Jeffries, Eric M; Allen, Robert A; Gao, Jin et al. (2015) Highly elastic and suturable electrospun poly(glycerol sebacate) fibrous scaffolds. Acta Biomater 18:30-9
Jeffries, Eric M; Nakamura, Shintaro; Lee, Kee-Won et al. (2014) Micropatterning electrospun scaffolds to create intrinsic vascular networks. Macromol Biosci 14:1514-20
Bae, Hojae; Chu, Hunghao; Edalat, Faramarz et al. (2014) Development of functional biomaterials with micro- and nanoscale technologies for tissue engineering and drug delivery applications. J Tissue Eng Regen Med 8:1-14
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
Johnson, Noah R; Wang, Yadong (2014) Coacervate delivery systems for proteins and small molecule drugs. Expert Opin Drug Deliv 11:1829-32

Showing the most recent 10 out of 28 publications