Biochemomechanics of intraluminal thrombus in abdominal aortic aneurysms.

Most computational models of abdominal aortic aneurysms address either the hemodynamics within the lesion or the mechanics of the wall. More recently, however, some models have appropriately begun to account for the evolving mechanics of the wall in response to the changing hemodynamic loads. Collectively, this large body of work has provided tremendous insight into this life-threatening condition and has provided important guidance for current research. Nevertheless, there has yet to be a comprehensive model that addresses the mechanobiology, biochemistry, and biomechanics of thrombus-laden abdominal aortic aneurysms. That is, there is a pressing need to include effects of the hemodynamics on both the development of the nearly ubiquitous intraluminal thrombus and the evolving mechanics of the wall, which depends in part on biochemical effects of the adjacent thrombus. Indeed, there is increasing evidence that intraluminal thrombus in abdominal aortic aneurysms is biologically active and should not be treated as homogeneous inert material. In this review paper, we bring together diverse findings from the literature to encourage next generation models that account for the biochemomechanics of growth and remodeling in patient-specific, thrombus-laden abdominal aortic aneurysms.

A 3-D Framework for Arterial Growth and Remodeling in Response to Altered Hemodynamics.

We present a three-dimensional mathematical framework for modeling the evolving geometry, structure, and mechanical properties of a representative straight cylindrical artery subjected to changes in mean blood pressure and flow. We show that numerical predictions recover prior findings from a validated two-dimensional framework, but extend those findings by allowing effects of transmural gradients in wall constituents and vasoactive molecules to be simulated directly. Of particular note, we show that the predicted evolution of the residual stress related opening angle in response to an abrupt, sustained increase in blood pressure is qualitatively similar to measured changes when one accounts for a nonlinear transmural distribution of pre-stretched elastin. We submit that continuum-based constrained mixture models of arterial adaptation hold significant promise for deepening our basic understanding of arterial mechanobiology and thus for designing improved clinical interventions to treat many different types of arterial disease and injury.

A mathematical model of evolving mechanical properties of intraluminal thrombus.

Quantifying mechanical properties of blood clots is fundamental to understanding many aspects of cardiovascular disease and its treatment. Nevertheless, there has been little attention to quantifying the evolving composition, structure and properties when a clot transforms from an initial fibrin-based mesh to a predominantly collagenous mass. Although more data are needed to formulate a complete mathematical model of the evolution of clot properties, we propose a general constrained mixture model based on diverse data available from in vitro tests on fibrinogenesis, the stiffness of fibrin gels, and fibrinolysis as well as histological and mechanical data from clots retrieved from patients at surgery or autopsy. In particular, albeit resulting from complex kinetics involving many clotting factors, we show that the rapid (minutes) in vitro production of fibrin from fibrinogen can be modeled well by an Avrami-type relation and similarly that the fast (tens of minutes) in vitro degradation of fibrin in response to different concentrations of plasmin can be captured via a single "master function" parameterized by appropriate half-times that can be inferred from laboratory or clinical data. Accounting simultaneously for the production and removal of fibrin as well as chemo-mechano-stimulated production of fibrillar collagens yields predictions of changing mass fractions and bulk mechanical properties that correspond well to experimentally available data. Constrained mixture models thus hold considerable promise for modeling the biomechanics of clot evolution and can guide the design and interpretation of needed experiments and stress analyses.