A two-scale numerical study on the mechanobiology of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are a serious condition whose pathophysiology is related to phenomena occurring at different length scales. To gain a better understanding of the disease, this work presents a multi-scale computational study that correlates AAA progression with microstructural and mechanical alterations in the tissue. Macro-scale geometries of a healthy aorta and idealized aneurysms with increasing diameter are developed on the basis of existing experimental data and subjected to physiological boundary conditions. Subsequently, microscopic representative volume elements of the abluminal side of each macro-model are employed to analyse the local kinematics at the cellular scale. The results suggest that the formation of the aneurysm disrupts the micromechanics of healthy tissue, which could trigger collagen growth and remodelling by mechanosensing cells. The resulting changes to the macro-mechanics and microstructure of the tissue seem to establish a new homeostatic state at the cellular scale, at least for the diameter range investigated.

Multiscale simulations suggest a protective role of neo-adventitia in abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are a dangerous cardiovascular disease, the pathogenesis of which is not yet fully understood. In the present work a recent mechanopathological theory, which correlates AAA progression with microstructural and mechanical alterations in the tissue, is investigated using multiscale models. The goal is to combine these changes, within the framework of mechanobiology, with possible mechanical cues that are sensed by vascular cells along the AAA pathogenesis. Particular attention is paid to the formation of a 'neo-adventitia' on the abluminal side of the aortic wall, which is characterized by a highly random (isotropic) distribution of collagen fibers. Macro- and micro-scale results suggest that the formation of an AAA, as expected, perturbs the micromechanical state of the aortic tissue and triggers a growth and remodeling (G&R) reaction by mechanosensing cells such as fibroblasts. This G&R then leads to the formation of a thick neo-adventitia that appears to bring the micromechanical state of the tissue closer to the original homeostatic level. In this context, this new layer could act like a protective sheath, similar to the tunica adventitia in healthy aortas. This potential 'attempt at healing' by vascular cells would have important implications on the stability of the AAA wall and thus on the risk of rupture. STATEMENT OF SIGNIFICANCE: Current clinical criteria for risk assessment in AAAs are still empirical, as the causes and mechanisms of the disease are not yet fully understood. The strength of the arterial tissue is closely related to its microstructure, which in turn is remodeled by mechanosensing cells in the course of the disease. In this study, multiscale simulations show a possible connection between mechanical cues at the microscopic level and collagen G&R in AAA tissue. It should be emphasized that these micromechanical cues cannot be visualized in vivo. Therefore, the results presented here will help to advance our current understanding of the disease and motivate future experimental studies, with important implications for AAA risk assessment.