Date of Award

12-2010

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Bioengineering

Advisor

Vyavahare, Naren

Committee Member

Ramamurthi , Anand

Committee Member

Gao , Bruce

Abstract

Valve disease is a specialized form of cardiovascular disease that specifically affects the heart valves. Heart valves serve the vital function of maintaining unidirectional blood flow through the chambers of the heart during the cardiac cycle; however, as valve disease progresses, this function can become severely compromised [1]. Currently, the only cure for valve disease is to replace the defective valve with an engineered substitute. Each year, over 300,000 heart valve replacement surgeries are performed worldwide [2], and this number is expected to continue growing as life expectancies increase [3].
In the United States, the most common form of valve disease is aortic stenosis [4], which can become severe enough to necessitate valve replacement surgery. Although the demand for replacement valves is growing, current clinically available valve substitutes have still not been perfected. Mechanical valves present problems with thrombosis and necessitate lifetime anticoagulation therapy, whereas bioprosthetic valves have limited durability [1, 5]. Furthermore, valve replacement surgery is very invasive, and high risk patient populations are often denied surgery. Over 50% of elderly populations with aortic stenosis are not offered surgery because the mortality risk is too great [6, 7].
Due to the limitations of traditional heart valve replacement surgery, a new, less invasive option, percutaneous aortic valve replacement (PAVR), has been developed [8, 9]. PAVR involves transcatheter delivery of a crimped, stented valve to the aortic annulus. The valve is deployed by a balloon catheter or self-expansion. While not yet commercially available, two percutaneous heart valves (PVRs) are currently in clinical trials [9]. These models are composed of glutaraldehyde-fixed pericardial tissue.
A major limitation of PVRs is the diameter to which the stent can be crimped. The device profile precludes use in small or tortuous vascular systems, limiting the candidate patient pool for PAVR [10]. An alternative material for PHVs may be porcine vena cava, as this tissue may provide enhanced flexibility and resilience. This study evaluates the feasibility of utilizing vena cava as a bioprosthetic tissue in PHVs by comparing its structural, mechanical, and in vivo properties to those of bovine pericardium. While the extracellular matrix fibers of pericardium are randomly oriented, the vena cava contains highly aligned collagen and elastin fibers that impart strength to the vessel in the circumferential direction and elasticity in the longitudinal. Mechanically, the vena cava is significantly less stiff than the pericardium, even after crosslinking with glutaraldehyde (GLUT) or combined neomycin and glutaraldehyde (NG) protocols. Furthermore, the vena cava's mechanical compliance is preserved after compression under forces similar to those exerted by a stent, whereas pericardium is significantly stiffened by this process. However, the high elastin content of the vena cava may be responsible for enhanced calcification as compared to the pericardium, and an effective anticalcification strategy is necessary if the vena cava is to be clinically useful. Taken together, these results suggest that the vena cava may enhance leaflet flexibility, tissue resilience, and tissue integrity in PHVs, ultimately reducing the device profile while improving the durability of these valves.

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