Histology-informed multiscale modeling of human brain white matter.

In this study, we propose a novel micromechanical model for the brain white matter, which is described as a heterogeneous material with a complex network of axon fibers embedded in a soft ground matrix. We developed this model in the framework of RVE-based multiscale theories in combination with the finite element method and the embedded element technique for embedding the fibers. Microstructural features such as axon diameter, orientation and tortuosity are incorporated into the model through distributions derived from histological data. The constitutive law of both the fibers and the matrix is described by isotropic one-term Ogden functions. The hyperelastic response of the tissue is derived by homogenizing the microscopic stress fields with multiscale boundary conditions to ensure kinematic compatibility. The macroscale homogenized stress is employed in an inverse parameter identification procedure to determine the hyperelastic constants of axons and ground matrix, based on experiments on human corpus callosum. Our results demonstrate the fundamental effect of axon tortuosity on the mechanical behavior of the brain's white matter. By combining histological information with the multiscale theory, the proposed framework can substantially contribute to the understanding of mechanotransduction phenomena, shed light on the biomechanics of a healthy brain, and potentially provide insights into neurodegenerative processes.

A two-scale numerical study on the mechanobiology of abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are a serious condition whose pathophysiology is related to phenomena occurring at different length scales. To gain a better understanding of the disease, this work presents a multi-scale computational study that correlates AAA progression with microstructural and mechanical alterations in the tissue. Macro-scale geometries of a healthy aorta and idealized aneurysms with increasing diameter are developed on the basis of existing experimental data and subjected to physiological boundary conditions. Subsequently, microscopic representative volume elements of the abluminal side of each macro-model are employed to analyse the local kinematics at the cellular scale. The results suggest that the formation of the aneurysm disrupts the micromechanics of healthy tissue, which could trigger collagen growth and remodelling by mechanosensing cells. The resulting changes to the macro-mechanics and microstructure of the tissue seem to establish a new homeostatic state at the cellular scale, at least for the diameter range investigated.

Multiscale simulations suggest a protective role of neo-adventitia in abdominal aortic aneurysms.

Abdominal aortic aneurysms (AAAs) are a dangerous cardiovascular disease, the pathogenesis of which is not yet fully understood. In the present work a recent mechanopathological theory, which correlates AAA progression with microstructural and mechanical alterations in the tissue, is investigated using multiscale models. The goal is to combine these changes, within the framework of mechanobiology, with possible mechanical cues that are sensed by vascular cells along the AAA pathogenesis. Particular attention is paid to the formation of a 'neo-adventitia' on the abluminal side of the aortic wall, which is characterized by a highly random (isotropic) distribution of collagen fibers. Macro- and micro-scale results suggest that the formation of an AAA, as expected, perturbs the micromechanical state of the aortic tissue and triggers a growth and remodeling (G&R) reaction by mechanosensing cells such as fibroblasts. This G&R then leads to the formation of a thick neo-adventitia that appears to bring the micromechanical state of the tissue closer to the original homeostatic level. In this context, this new layer could act like a protective sheath, similar to the tunica adventitia in healthy aortas. This potential 'attempt at healing' by vascular cells would have important implications on the stability of the AAA wall and thus on the risk of rupture. STATEMENT OF SIGNIFICANCE: Current clinical criteria for risk assessment in AAAs are still empirical, as the causes and mechanisms of the disease are not yet fully understood. The strength of the arterial tissue is closely related to its microstructure, which in turn is remodeled by mechanosensing cells in the course of the disease. In this study, multiscale simulations show a possible connection between mechanical cues at the microscopic level and collagen G&R in AAA tissue. It should be emphasized that these micromechanical cues cannot be visualized in vivo. Therefore, the results presented here will help to advance our current understanding of the disease and motivate future experimental studies, with important implications for AAA risk assessment.

Numerical study on the effect of stent shape on suture forces in stent-grafts.

Second-generation stent-grafts (SGs) have addressed many of the mechanical problems reported for first-generation endoprostheses, such as graft tear and stent rupture; however, suture wear and detachment due to pulsatile fatigue remains an issue. Numerical studies on the mechanical behavior of these endoprostheses usually model the attachment between stents and graft as a continuous ''tie'' constraint, which does not provide information on the mechanical loads acting on individual sutures. This paper presents a suitable approach for Finite Element (FE) simulations of SGs which allows for a qualitative evaluation of the loads acting on sutures. Attachment between stents and graft is modeled as rigid beams at discrete locations of the endoprostheses, and the reaction forces on the beams are analyzed. This modeling strategy is employed for four different SG models (two Z-stented commercial models and two circular-stented models) subjected to a severe 180° U-bend, followed by intraluminal pressurization. Results show that, for all models, the majority of sutures is experiencing fluctuating forces within a cardiac cycle (between 80 and 120 mmHg), which points to pulsatile fatigue as potential failure mode. In addition, the highest loads are concentrated in kinks and, for Z-stented models, at the apexes of stents. Moreover, suture loads for circular-stented models are lower than for Z-stented models, indicating better resistance to suture detachment. All these observations are in line with experimental results published in the literature, and, therefore, the procedure herein proposed may serve as a valuable tool in the development of new SG models with better suture resistance to pulsatile wear and fatigue.