Date of Award

12-2010

Document Type

Dissertation

Degree Name

Doctor of Philosophy (PhD)

Legacy Department

Bioengineering

Advisor

Simionescu, Dan T

Committee Member

Burg , Karen

Committee Member

Ramamurthi , Anand

Committee Member

Isenburg , Jason

Abstract

The Cardiovascular diseases (CVDs) continue to be the leading cause of morbidity and mortality worldwide. The most common form of CVDs is occlusion of blood flow thus limiting blood supply to specific tissues or organs. Atherosclerosis is a leading cause of coronary heart disease and stroke, which were responsible for more than 25% of deaths in 2004.
The demand for vascular graft is huge. In United States alone, approximately 500,000 coronary artery bypass graft surgeries are performed annually. Synthetic polymers such as Dacron and ePTFE have been successfully applied in large diameter blood vessel prosthesis; however, for small diameter (inner diameter < 6mm) blood vessel replacement, both performed poorly in small diameter indications. Autologous saphenous vein or internal mammary artery remains the gold standard. However, autologous vessel is not available in about 1/3 of the patients.
We proposed a novel biological scaffold based on decellularization of porcine arteries. Decellularized arterial scaffolds were further stabilized with penta-galloyl glucose (PGG) to render it more resistant to rapid in vivo biodegradation. The resultant scaffolds had good mechanical properties in burst pressure and vascular compliance. Subdermal implantation study showed that our novel scaffolds were biocompatible, inductive to host cell repopulation and had good remodeling potential.
A dynamic cell seeding device which is capable of utilizing three different mechanisms was designed and built to endothelialize luminal surface of grafts. Of three mechanisms, electrical field and hydrostatic pressure seeding methods resulted in overall good cell coverage, while chemotaxis was the least efficient.
We further developed a pulsatile vascular bioreactor to test endothelial cells retention under pulsatile flow. Grafts expanded and recoiled in response to the pulsatile flow created by the pinch valve periodically opening/closing at 1Hz. We found that seeded endothelial cells could withstand to 20h of pulsation and stayed alive, as shown in the DiffQuik and Live/Dead staining results.
In collaboration with researchers in Japan & South Africa, we tested the functionality of our PGG-stabilized scaffolds using animal circulation models. Vascular graft of about 5 cm long was anastomosed to host artery in end-to-end fashion. Preliminary data showed that our novel acellular vascular scaffolds were very inductive to host cell repopulation. Heparinized grafts remained patent after 7 days.

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