Date of Award

Fall 2022

Document Type

Open Access Dissertation

Department

Biomedical Engineering

First Advisor

John F. Eberth

Abstract

Coronary artery disease is a localized form of atherosclerosis that can severely restrict blood flow to the heart often requiring a surgical intervention known as coronary artery bypass grafting (CABG) to reestablish perfusion to this essential circulation. To some extent, the selection of the autograft tissue is at the surgeon’s discretion with factors such as stenosis location and the existing tissue’s pathological state contributing to a choice that could be deterministic in surgical outcomes. Many post-operative complications and premature graft failures originate from graft-target tissue incompatibilities and altered blood flow patterns. We hypothesize that mechanical mismatching between the graft material and the host tissue contributes to the loss of patency following CABG - even when using internal thoracic arteries (ITA), the clinical benchmark for autologous bypass grafting. To that end we have quantified the spatially heterogeneous mechanical properties of left (L) and right (R) ITAs using a porcine surrogate for the human vasculature. Biaxial mechanical testing revealed significantly larger circumferential stresses and lumen area compliances in the proximal region of LITAs, while the distal region of RITAs exhibited significantly larger axial stresses. In addition, we captured significant histological differences in the elastin-collagen aspect ratio throughout both arteries. The relative amounts of these load-bearing constituents are known to influence the local mechanical behavior and therefore our histological observations support the captured biaxial mechanical data. We then performed a similar tissue characterization study to quantify the properties of four distinct coronary arteries that are common targets for CABG procedures. Our findings indicate that these blood vessels are classified as muscular arteries, and they possess distinctly different histological features and a unique mechanical behavior.

Patients that require secondary CABG surgery do not always have suitable autologous vessels available to serve as grafts. Decellularized vascular grafts (DCVGs) have emerged as a functional alternative to autologous bypass grafting. Despite the inherent advantage of removing immunogenic materials to mitigate host rejection, thrombosis, restenosis, and aneurysm formation limit the widespread usage of DCVGs. However, surgical dependence on autologous grafts presents a need for the effective preservation of unused or excised graft vessels that can be implanted in CABG surgeries. Likewise, cryopreservation techniques have been developed to circumvent unwanted biological and physical consequences through controlled media exchange and regulated freezing conditions. These techniques can be modified to aid in the development of graft tissue banks that can be used to alleviate graft shortages. However, the consequences of decellularization and cryopreservation techniques on elastomuscular artery mechanical properties and microarchitecture warrant further investigation since extracellular matrix proteins and water content contribute to the gross properties of all soft-biological tissues.

Thus, this dissertation offers quantified data of the distinctly different histomechanical metrics that exist along the length of the superior CABG candidate, the ITA. Our finite element models of the end-to-end anastomoses reveal that these different regions produce varying hemodynamic and solid mechanical stress magnitudes. These findings offer predictions of mechanobiological complications and grafting outcomes, thereby contributing fundamental evidence to the fields of experimental and computational vascular biomechanics. Lastly, the work presented in this dissertation provides quantified evidence of different decellularization and cryopreservation methods that minimize biochemical and biomechanical consequences. Overall, these findings contribute to the fields of tissue engineering and vascular mechanics by exploring strategies and techniques that produce optimal decellularization or cryopreservation outcomes.

Rights

© 2022, Colton J. Kostelnik

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