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Nanoindentation test
Nanoindentation tests may be used to characterize local deformation and properties in multilayer materials
[Figure 1F]. Though it is known that the artery is made up of three distinct layers, a large portion of
the aorta’s biomechanical modelling describe it as a single, homogenous layered vessel. That being said,
experimental results regarding the behaviour of the individual layers has been performed on ATAA
tissue in detail, and strain-energy-functions were fit to the data to describe the behaviour. Reiterating the
discussion from Uniaxial Testing, it was shown that the intima was the weakest of the three layers, with
the adventitia exhibiting the highest failure stresses and resistance to excessive deformation, preventing
[10]
rupture. Sokolis et al. revealed that the behaviour of the intact aneurysmal wall was most similar to the
intima and media layers, however, drawing inferences regarding the overall layered vessel wall behaviour
remains a challenge due to the complex attachment and interaction between layers.

[41]
Hemmasizadeh et al. introduced a custom nanoindentation technique showing that the inner layer is
more compliant than the outer layer and sustains higher strains. Therefore, rupture of the aorta travels
[42]
outwards from the inner layer. This is verified by Manopoulos et al. by uniaxial tests performed on
ascending thoracic aortic dissected tissue to understand the failure properties for the vessel wall as divided
into an inner (intima-media) and outer (media-adventitia) layer. They found that the inner layer displayed
a significantly lower strength than the outer layer, in addition to a sharp decline of stress following rupture,
unlike the outer layer which exhibited a slow decrease to zero stress. Interestingly, the relative strengths of
the two layers differed significantly in magnitude from what has previously been reported on the individual
layers [10,42] . The outer layer was shown to be stronger than the adventitia alone, and in comparing the
properties of the origin of inner layer failure to distal locations, it was evident that dissection occurred
where the layer was thinner and exhibited increased stiffness. These results offer valuable insight as to why
[42]
the specimens studied dissected, rather than undergoing full rupture.

FACTORS AFFECTING ARTERIAL MECHANICS
Histological effects
Soft tissues, including blood vessels, contain collagen, elastin, and ground substance. The relative amount,
density, and arrangement of these three constituents greatly affect the mechanical response of the
tissue [43,44] . Therefore, it is important to consider histological composition when characterizing the physical
properties of the aortic wall. Distribution of elastic fibres in soft tissues and its relation to mechanical
[18]
properties have been studied extensively [43,45] . Bellini et al. better defined the mechanical environments
of the media and adventitia layers within the arterial wall by highlighting the roles that smooth muscle
[46]
cells and fibroblasts play in arterial homeostasis. Taghizadeh et al. evaluated the mechanical properties
[36]
of the aortic wall while accounting for the lamellar structure within the media layer. Cardamone et al.
confirmed that elastin contributes significantly to the shortening of arteries observed upon cutting along
the circumferential direction (residual stresses), and to the opening angle phenomenon. Holzapfel et al. [47]
combined histological data with computational modelling to create a general constitutive model of the
anisotropic collagen fibre dispersion in arterial walls. In terms of aneurysmal tissue, studies focusing on the
ascending aorta report reduced levels of elastin, but normal levels of collagen, throughout the vessel wall
when compared to a healthy aorta [48,49] . Aneurysm development in the ascending aorta has been shown
to be associated with higher stiffness of the wall, resulting in increased wall stresses, but not leading to a
[48]
weakening of the wall for age-matched subjects .
Segmental effects
There are segmental differences in the structure and mechanical properties of the aorta, and these are
dependent on the magnitude of stress that the wall is subjected to regularly under normal conditions.
[50]
Schriefl et al. incorporated the themes of segmental and histological analysis to study the layer specific
distribution and orientation of collagen fibres in the abdominal and thoracic aorta. They concluded that