Exploring blood clot mechanics : scientific and educational tools for comprehensive understanding

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2023-12

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Abstract

Venous thromboembolism, encompassing deep vein thrombosis and pulmonary embolism, poses a significant global health burden, impacting millions of lives each year. A key determinant of patient outcomes in thromboembolic disease is the occurrence of embolization – or of small clot pieces breaking off. Embolization risk is not currently well understood, and clinical care for thrombi is not informed by clot-specific factors. In order to stratify embolic risk, we must first understand blood clot as a material and the factors which contribute to its ability to resist fracture. This is a challenging problem, as in vivo thrombi are difficult if not impossible to access nondestructively, heterogeneous, and irregular in size and shape. As such, in vitro blood clot mimic models are often used as a proxy for in vivo thrombi. In this dissertation, we first develop an experimental framework to rigorously characterize the mechanics of whole blood clots. We first approximated their behavior as hyperelastic using simple shear testing, simultaneously determining the effects of experimental factors like blood storage and coagulation time on clots’ mechanics. Through this study we determined that blood clot has strongly nonlinear mechanics and its hyperelastic behavior is well described using the Ogden model. Secondly, we examined the dissipative mechanisms which arise prior to fracture in a pure shear geometry. We describe that clots are viscoelastic, demonstrating strain-rate dependence, hysteresis, Mullins-like effect, and nonlinear stress relaxation. Third, we compared the viscoelastic and fracture behavior of clots made from human and bovine blood. We found that, compared to bovine clots, clots made from human blood are weaker, softer, and less resistant to fracture, among other differences. Finally, we developed a low-cost, openly-available mechanical testing device and employed it as a teaching tool in a college-level biomechanics course as well as two elementary-level outreach activities. Altogether, this dissertation contributes to our collective understanding of venous thromboembolism and offers resources for communicating the importance of biomechanics to the public.

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