# Heterogeneity of Ex Vivo and In Vivo Properties along the Length of the Abdominal Aortic Aneurysm
## 4 Discussion  
The present study aimed at investigating the structural and biomechanical heterogeneity of aortic aneurysl tissue, with respect to the position along the length and circumference of the artery. Both invasive and non-invasive image-based measures were performed on regions of AAAs for a population of patients referred to elective surgery. Specifically, open repair surgery involving complete aortic resection allowed for the collection of tissue specimens from different regions along the aorta, enabling the ex vivo regional characterization of the aneurysl tissue by means of biaxial testing, with novel biaxial parameters and histological analysis. It is important to note that studies on the ex vivo characterization of aneurysl tissue often focus on one specimen as representative of the aneurysm or on few samples mostly collected from the anterior portion of the aorta [12]. For this reason, research dealing with regional differences has often been carried out on animal models in order to compensate for the limited availability of human tissue [14; 15]. Biaxial mechanical testing of AAA tissue enables accurate assessment of the coupling of fibers in two orthogonal directions--and thus of anisotropy--spanning a range of physiological stresses/strains. However, studies focusing on biaxial testing are scarce due to aneurysl tissue fragility. In our study, more than 30% specimens failed before reaching the 40% displacement protocol. The remaining specimens required extremely delicate handling. Alterations in the biomechanical properties of the AAA are attributed to the changes in the structure of the extracellular matrix (ECM) constituents, mainly the elastin and collagen fibers. The low-strain tangential modulus (LTM) is associated with the behavior at low strain often attributed to the elastin component. The onset stress at the beginning of the transition zone (TZo) marks the instant when the collagen begins to engage and resist the applied loading. The end of the transition zone (TZe) is indicative of the collagen in the tissue being fully activated and the transition from the elastin-dominated mechanical response to the collagen-dominated response is complete. Finally, the high-strain tangential modulus (HTM) captures the fully engaged collagen-associated behavior. The LTM was the only mechanical parameter found to be significantly affected by the position along the circumference of the AAA. The LTM is associated with the elastin-dominated region of aortic tissue behavior. Thus, this asymmetry could be associated with varying distributions of elastin content. In fact, the left patches of AAAs were found to have higher elastin content, which was clearly reflected in the biaxial data showing higher LTM in the left-anterior (LA) and left-posterior (LP) regions. Similarly, histological samples collected from posterior regions showed higher elastin content reflected in the trend towards higher LTM for posterior biaxial specimens. Interestingly, significant differences in LTM were associated with opposing circumferential regions. Other studies also reported the heterogeneity along the circumferential regions of the aorta [11; 37]. However, their assessment was based on uniaxial biomechanical parameters, and thus, their results are true for the high-strain mechanical response only with no consideration for the coupling of fibers in two orthogonal directions. The present study, to the best of the authors' knowledge, is the first to report circumferential heterogeneity at the low strain regime (LTM). Regarding the axial heterogeneity, there was no effect of the position along the length of the aorta on LTM values, potentially due to the higher variability in LTM, especially in the aneurysl sac (position 3 and 4). The present results show that the collagen-related biaxial properties TZo, TZe, and HTM in the circumferential direction were significantly different for tissue samples collected from different regions along the length of the AAA (positions 1 to 6).