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An in Vitro Approach to Vascular Therapeutic Testing
by
Hasanain, Shahd Ali
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Biomedical engineering
2021
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An in Vitro Approach to Vascular Therapeutic Testing
by
Hasanain, Shahd Ali
in
Biomedical engineering
2021
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Dissertation
An in Vitro Approach to Vascular Therapeutic Testing
2021
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Overview
Aortopathies refer to a broad class of pathological conditions affecting the aorta and are a major cause of morbidity and mortality in the US. Specifically, aortic aneurysms and aortic dissections have diverse etiologies that are initiated by alterations in the tissue’s extra-cellular-matrix (ECM) proteins, namely collagen and elastin, thereby predisposing the aortic wall to weaken and rupture. Pentagalloyl glucose (PGG) has recently emerged as a non-surgical treatment to reduce the risk of dissection or rupture. PGG is a known antioxidant and anti-inflammatory and has been shown to have ECM-restorative qualities that enhance collagen and elastin’s functional properties. Prior studies using PGG were largely performed in vivo or acutely in vitro; here, we aim to create a controllable, repeatable, fast, and inexpensive in vitro experimental platform to allow testing of this and other vascular therapeutics. To that end, we first created and validated the in vitro platform by assuring that cultured aortas maintained viability and mechanical properties for up to 2 weeks using multiple freely floating and stress-free configurations within an oscillating bioreactor. Next, we used this platform to investigate the effect of PGG on otherwise healthy thoracic aortas. Finally, we used tissues taken from a genetic mouse model of elastin damage, Marfan Syndrome (Fbn1C1039G/+), to test PGG’s restorative capability on diseased aortas.
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