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Register a new userReview of the Essential Roles of SMCs in ATAA Biomechanics
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Authors
Claudie Petit
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Aortic Aneurysms are among the most critical cardiovascular diseases. The present study is focused on Ascending Thoracic Aortic Aneurysms (ATAA). The main causes of ATAA are commonly cardiac malformations like bicuspid aor-tic valve or genetic mutations. Research studies dedicated to ATAA tend more and more to invoke multifactorial eects. In the current review, we show that all these eects converge towards a single paradigm relying upon the crucial biome-chanical role played by smooth muscle cells (SMCs) in controlling the distribution of mechanical stresses across the aortic wall. The chapter is organized as follows. In section 6.2, we introduce the basics of arterial wall biomechanics and how the stresses are distributed across its dierent layers and among the main structural constituents: collagen, elastin, and SMCs. In section 6.3, we introduce the biome-chanical active role of SMCs and its main regulators. We show how SMCs actively regulate the distribution of stresses across the aortic wall and among the main structural constituents. In section 6.4, we review studies showing that SMCs tend to have a preferred homeostatic tension. We show that mechanosensing can be understood as a reaction to homeostasis unbalance of SMC tension. Through the use of layer-specic multiscale modeling of the arterial wall, it is revealed that the quantication of SMC homeostatic tension is crucial to predict numerically the initiation and development of ATAA.
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Vehicle safety systems have substantially decreased motor vehicle crash-related injuries and fatalities, but injuries to the lumbar spine still have been reported. Experimental and computational analyses of upright and, particularly, reclined occupants in frontal crashes have shown that the lumbar spine can be subjected to axial compression followed by combined compression-flexion loading. Lumbar spine failure tolerance in combined compression-flexion has not been widely explored in the literature. Therefore, the goal of this study was to measure the failure tolerance of the lumbar spine in combined compression and flexion. Forty 3-vertebra lumbar spine segments were pre-loaded with axial compression and then subjected to dynamic flexion bending until failure. Clinically relevant middle vertebra fractures were observed in twenty-one of the specimens, including compression and burst fractures. The remaining nineteen specimens experienced failure at the potting grip interface. Since specimen characteristics and pre-test axial load varied widely within the sample, failure forces (mean 3.4 kN, range 1.6-5.1 kN) and moments (mean 73 Nm, range 0-181 Nm) also varied widely. Tobit univariate regressions were performed to determine the relationship between censored failure tolerance and specimen sex, segment type (upper/lower), age, and cross-sectional area. Age, sex, and cross-sectional area significantly affected failure force and moment individually (p<0.0024). These data can be used to develop injury prediction tools for lumbar spine fractures and further research in future safety systems.
In its permanent quest of mechanobiological homeostasis, our vascula-ture significantly adapts across multiple length and time scales in various physiological and pathological conditions. Computational modeling of vascular growth and remodeling (G&R) has significantly improved our insights of the mechanobio-logical processes of diseases such as hypertension or aneurysms. However, patient-specific computational modeling of ascending thoracic aortic aneurysm (ATAA) evolution, based on finite-element models (FEM), remains a challenging scientific problem with rare contributions, despite the major significance of this topic of research. Challenges are related to complex boundary conditions and geometries combined with layer-specific G&R responses. To address these challenges, in the current paper, we employed the constrained mixture model (CMM) to model the arterial wall as a mixture of different constituents such as elastin, collagen fiber families and smooth muscle cells (SMCs). Implemented in Abaqus as a UMAT, this first patient-specific CMM-based FEM of G&R in human ATAA was first validated for canonical problems such as single-layer thick-wall cylindrical and bi-layer thick-wall toric arterial geometries. Then it was used to predict ATAA evolution for a patient-specific aortic geometry, showing that the typical shape of an ATAA can be simply produced by elastin proteolysis localized in regions of deranged hemodymanics. The results indicate a transfer of stress to the adventitia by elastin loss and continuous adaptation of the stress distribution due to change of ATAA shape. Moreover, stress redistribution leads to collagen deposition where the maximum elastin mass is lost, which in turn leads to stiffening of the arterial wall. As future work, the predictions of this G&R framework will be validated on datasets of patient-specific ATAA geometries followed up over a significant number of years.
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