Mechano-biology in the thoracic aortic aneurysm: a review and case study.

An aortic aneurysm is a permanent and localized dilatation of the aorta resulting from an irreversible loss of structural integrity of the aortic wall. The infrarenal segment of the abdominal aorta is the most common site of aneurysms; however, they are also common in the ascending and descending thoracic aorta. Many cases remain undetected because thoracic aortic aneurysms (TAAs) are usually asymptomatic until complications such as aortic dissection or rupture occurs. Clinical estimates of rupture potential and dissection risk, and thus interventional planning for TAAs, are currently based primarily on the maximum diameter and growth rate. The growth rate is calculated from maximum diameter measurements at two subsequent time points; however, this measure cannot reflect the complex changes of vessel wall morphology and local areas of weakening that underline the strong regional heterogeneity of TAA. Due to the high risks associated with both open and endovascular repair, an intervention is only justified if the risk for aortic rupture or dissection exceeds the interventional risks. Consequently, TAAs clinical management remains a challenge, and new methods are needed to better identify patients for elective repair. We reviewed the pathophysiology of TAAs and the role of mechanical stresses and mathematical growth models in TAA management; as a proof of concept, we applied a multiscale biomechanical analysis to a case study of TAA.

A microstructurally motivated model of arterial wall mechanics with mechanobiological implications.

Through mechanobiological control of the extracellular matrix, and hence local stiffness, smooth muscle cells of the media and fibroblasts of the adventitia play important roles in arterial homeostasis, including adaptations to altered hemodynamics, injury, and disease. We present a new approach to model arterial wall mechanics that seeks to define better the mechanical environments of the media and adventitia while avoiding the common prescription of a traction-free reference configuration. Specifically, we employ the concept of constituent-specific deposition stretches from the growth and remodeling literature and define a homeostatic state at physiologic pressure and axial stretch that serves as a convenient biologically and clinically relevant reference configuration. Information from histology and multiphoton imaging is then used to prescribe structurally motivated constitutive relations for a bi-layered model of the wall. The utility of this approach is demonstrated by describing in vitro measured biaxial pressure-diameter and axial force-length responses of murine carotid arteries and predicting the associated intact and radially cut traction-free configurations. The latter provides a unique validation while confirming that this constrained mixture approach naturally recovers estimates of residual stresses, which are fundamental to wall mechanics, without the usual need to prescribe an opening angle that is only defined conveniently on cylindrical geometries and cannot be measured in vivo. Among other findings, the model suggests that medial and adventitial stresses can be nearly uniform at physiologic loads, albeit at separate levels, and that the adventitia bears increasingly more load at supra-physiologic pressures while protecting the media from excessive stresses.

Stress-modulated remodeling of a non-homogeneous body.

Many soft tissues, and arteries in primis, exhibit residual stress after unloading, a characteristic related to the ability to self-organize their own constituents (cells and extracellular matrix proteins). This behavior can be theoretically predicted in a continuum mechanics framework assuming that the body self-remodels toward a homeostatic stress state. Open questions concern the characteristics of a stationary grown state, as dictated by the mechanical properties of the material and by the specific external load. In this paper, we illustrate a mathematical framework and we perform numerical simulations for the remodeling of a two-dimensional (axisymmetric) nonlinear elastic cylinder. In particular, we address the stress-modulated remodeling of the cylinder wall when local variations in the mechanical properties of the material occur. Our main result is that, as in one spatial dimension, the tendency of the system to homeostasis generates, thanks to the remodeling process, a residual stress that homogenizes the tension in the body under load. Possible physiological implications of this result are discussed in the final section.

Fluid-structure interaction within realistic three-dimensional models of the aneurysmatic aorta as a guidance to assess the risk of rupture of the aneurysm.

Abdominal aortic aneurysm (AAA) disease is a degenerating process whose ultimate event is the rupture of the vessel wall. Rupture occurs when the stresses acting on the wall rise above the strength of the AAA wall tissue. The complex mechanical interaction between blood flow and wall dynamics in a three dimensional custom model of a patient AAA was studied by means of computational coupled fluid-structure interaction analysis. Real 3D AAA geometry is obtained from CT scans image processing. The results provide a quantitative local evaluation of the stresses due to local structural and fluid dynamic conditions. The method accounts for the complex geometry of the aneurysm, the presence of a thrombus and the interaction between solid and fluid. A proven clinical efficacy may promote the method as a tool to determine factual aneurysm risk of rupture and aid the surgeon to refer elective surgery patients.