## 3 Results
### Aortic Wall Characterisation
#### 3.5.2 Wall Microstructure  
The aortic wall is a complex structure constituted by three distinct layers with distinct material properties, microstructure and morphology and adaptative to the mechanical environment. For instance, older patients present stiffer aortas resulting from increased collagen content and reduced elastin content. Another example of the nuances of this structure is how an elevated WSS magnitude deregulates matrix metalloproteinase synthesis, which contributes to the cleavage of collagen fibres and consequent weakening of the wall. Henceforth, studying the effects of the mechanical environment on the wall microstructure is relevant to a better understanding of the underlying mechanisms of the development of acute complications. In 2008, [PERSON] et al. [24] developed a CSM model using FEM that aimed to estimate aneurysmal diameter growth. They chose an adaptative constitutive model which considered collagen degradation in regions where the stress surpassed a certain threshold. Despite the elevated clinical interest in the presented model, no relevant results were presented due to the excessive number of limitations. [PERSON] et al. [36] created an aortic media lamellar model, constituted by adjacent stripes that alternated between representing elastic lamellae and the constituents comprising two elastic laminae, e.g., collagen fibres and vascular smooth muscle cells. For hypertensive pressure conditions (160 mmHg), the results suggested elastin as a major load-bearing component in lower strain regimes. Increased strain induces the engagement of collagen fibres, evidencing that these are the primary load-bearing component for higher strains. Moreover, the authors postulated that wall thickening and alteration of the microstructure promoted higher blood pressure. [PERSON] et al. [87] assessed the changes in the aortic wall microstructure, especially on collagen fibres, by imposing BC that recreated uniaxial tensile tests. CSM simulations on representative volumes of the aortic media were calculated. The heterogeneity in mechanical properties was found to increase with stretch, mainly due to the spatial orientation of collagen fibres and activation. In 2017, the same group [9] suggested that under these conditions, aortic tissue failure is governed by the cleavage of collagen fibres as they are stiffer and present inferior maximum stretch. Elastin fibres are more compliant, thus being the main contributor to hyperelastic behaviour of the aortic wall. \begin{table}
\begin{tabular}{c c c c c c c c c c c c c c} \hline \hline
**Fint Author** & **Year** & **Simulation** & **Solver** & **Geometry** & \begin{tabular}{c} **Boundary** \\ **Conditions** \\ \end{tabular}  & **Flow** & **Wall** & **Main Remarks** & **Aim of the Work** & **GRADE** \\ \hline G. & 2021 & FSI (FEM) & Abaqus & TA (PS-MRI) & 1 FP: OCP & L & N & O: HOG & & & & & & & & & &  
[PERSON] et al. [10] implemented an extension-inflation-torsion in silico test that intended to study the underlying mechanisms of the development and progression of AD. The numerical model used an anisotropic wall constitutive model and failure criterion. In-plane shear stress originating from the heterogeneity of aortic wall mechanical properties was found to be the main contributor to initial tearing [45] and the second blood flow on the FL the main contributor to AD progression. Similar to [PERSON] et al. [9], [PERSON] et al. [88] developed a CSM virtualisation of a mechanical test (biaxial tensile). The results also suggested cleavage of collagen fibres as the main contributor to the failure of the aortic wall. Under biaxial conditions, collagen fibres in both directions are similarly loaded and rupture is likely to occur in any direction as well. [PERSON] et al. [89] simulated peeling and direct tension tests, aiming to study the effect of glycation (covalent attachment of sugars, usually glucose, to a protein or lipid) on the interlamellar bonding properties of medial elastin, which is often compromised in CVD.