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Browsing by Subject "Mechanoadaptation"

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    Mechanical Heterogeneity and Mechanoadaptation in Cerebral Aneurysms
    (2022-12) Shih, Elizabeth
    Cerebral aneurysms are abnormal dilations of blood vessels in the brain found in 2% of the population. While rupture is rare, it is fatal or will most likely cause neurological deficits. The prevalence of unexpected ruptures suggests that the current predictive measurements to evaluate rupture risk are incomprehensive and require more investigation. To understand progression and stabilization versus rupture, we adopt a biomechanical approach to investigate how cellular mechanism influence tissue-scale mechanics. In my first aim, I mechanically characterize the local heterogeneity in acquired human cerebral aneurysm and arterial specimens using the Generalized Anisotropic Inverse Mechanics method. I find that both ruptured and unruptured aneurysms are considerably weaker and more heterogeneous than normal arteries, suggesting that maladaptive remodeling results in complex mechanical properties arising from initially ordered structures. From these changes, stress concentrations at boundaries between stiff and weak regions and diverse cell microenvironments are all likely to influence stabilization versus rupture. After identifying that aneurysms contain a wide range of microenvironment stiffnesses, I investigate how local extracellular stiffnesses influence the mechanically dominant and mechanosensitive vascular smooth muscle cells using cellular microbiaxial stretching. First, I examine the common assumptions used in inverse calculations of cell tractions and find that a crucial filtering term must be scaled accordingly to cell substrate mechanical properties to ensure accurate calculations. When this term is adjusted across different microenvironment/substrate groups, I find that healthy smooth muscle cells are remarkably robust across a wide range of substrate moduli. Lastly, I develop a continuum model to capture the physical forces exerted on single cells during aneurysm progression, in which cell density begins to decrease and cells are only able to remodel their immediate surroundings. The model introduces a strain factor for vascular smooth muscle cells, which combines the homogeneous rule-of-mixtures approach with an Eshelby-based strain factor to describe a single inclusion in an infinite matrix. This model will be incorporated into future growth and remodeling laws to describe aneurysm progression. Taken together, the results of this work elucidate the complex tissue and cell mechanics that govern aneurysm development, stabilization, and rupture. This provides a basis to eventually identify new metrics for risk evaluation and improve future predictive models for clinical translation, ultimately aiding aneurysm diagnoses and treatment plans.