Atherosclerosis is a widespread disease characterized by the formation of a plaque within the inner most layer of the arterial wall. This plaque is comprised of a lipid-rich pool containing little to no collagen covered by a collagenous fibrous cap which serves as a barrier containing the plaque from rupture. Plaque rupture is an often fatal phenomenon, not yet fully understood, which can result in arterial blockage causing myocardial infarction or stroke depending on rupture location. Whether a plaque will rupture depends on many interrelated aspects; the biological composition of the plaque, the mechanical properties of these components, and how they are mechanically loaded. The collagenous matrix is the main load bearing structure of the plaque cap, therefore affects plaque stability and should be further investigated. Due to the various limitations when studying ex vivo and in vivo human plaques as well as the significant difference in plaque development in animal models, an in vitro atherosclerotic plaque cap model is necessary to systematically study plaque rupture mechanics. In this study, a simplified collagenous fibrous cap model with a soft inclusion (SI) was developed. The effect of intermittent uniaxial straining (IS) versus no straining (static) during culture was investigated as intermittent straining during culture is linked to an increase in alignment of collagen fibers in the loading direction, which is seen in human fibrous caps. The constructs were mechanically tested with two different clamp designs (commercial and redesigned), to investigate the differences in mechanical behavior and to improve the clamping technique. The local strain patterns were studied using digital image correlation (DIC) preceding rupture. Although there was higher compaction observed in the IS constructs when compared to the static constructs, the mechanical behavior of the IS and static constructs tested in the commercial clamps were comparable. However, DIC analysis demonstrated that the static constructs in the commercial clamps showed homogeneous extension behavior, whereas the IS constructs showed a symmetric “C-shaped” compressive pattern, signifying a possible difference in microstructure. Additionally, the redesigned clamps displayed a consistent two bump rupture pattern correlating to rupture near the SI, as well as higher measured force at comparable stretch, not seen with the commercial clamps. The redesigned clamps demonstrated an improvement in the testing method when compared to the commercial clamps by exhibiting better load transmission from clamp to tissue, creating more homogeneous strain distribution within the region of interest and leading to more consistent rupture near the SI. Interestingly, high extension values were observed at the rupture location in both the redesigned and commercial clamps, possibly demonstrating a linkage between high extension behavior and rupture location. In this study, collagenous constructs with an integrated SI were successfully created exhibiting mechanical properties within the range found in literature and rupturing near the SI-tissue interface, therefore these findings can serve as a guide for future experiments in the development of an atherosclerotic plaque cap in vitro model.

The aortic valve is a valve made of three thin flexible leaflets which open and close in order to allow the unidirectional passage of blood from the left ventricle to the aorta. Because of this repetitive motion at each cycle, the valve is constantly exposed to large variations of pressure and hemodynamic forces. Deterioration in its peculiar functioning could lead to the arising of valvular diseases such as stenosis or regurgitation. A widely spread procedure to cure severely damaged heart valves is the replacement with artificial heart valves. However, up to now, the natural aortic valve properties and functionalities have never been equalised by any manufactured prototypes in terms of efficiency and durability. This limitation has inspired many engineering researches with the purpose of gaining a complete understanding on the working principles of the valve and the evolution of the flow through it in order to enhance the performances of these medical devices. In this thesis, numerical simulations of blood passing through the aortic valve have been performed. In particular, this study proposes an alternative investigating approach which consists on prescribing the rigid motion of the leaflets a priori as taken from experimental values and without the employment of the structural solver. To execute this strategy, the Arbitrary Lagrangian-Euler method along with remeshing techniques has been employed in Ansys Fluent. The main objectives concern the study of the resulting hemodynamics in the aortic root and the validation with other investigating techniques such as experimental work and Fluid-Structure Interaction simulations. First, the methodology was tested in a two-dimensional geometry which embodied a simplified representation of the aortic root. Secondly, a more realistic three-dimensional case was analysed with the employment of a commercial bileaflet mechanical valve. In this case, two different methods were adopted to deal with the transition of the flow to a turbulent regime. Namely, the analysis was conducted both by the resolution of the unsteady Reynolds-Averaged Navier-Stokes equations with the k-ε model and by maintaining a laminar approach. Validation of the method with available experimental data showed that the two-dimensional case is well reproduced. On the other hand, mainly qualitative agreement is obtained for the three-dimensional case. This suggests that the proposed approach is able to capture the main features of the flow to a certain extent and future investigations are required to obtain more accurate predictions of the flow.