The role of biomechanics in the assessment of carotid atherosclerosis severity: a numerical approach

Numerical fluid biomechanics has been proved to be an efficient tool for understanding vascular diseases including atherosclerosis. There are many evidences that atherosclerosis plaque formation and rupture are associated with blood flow behavior. In fact, zones of low wall shear stress are vivid areas of proliferation of atherosclerosis, and in particular, in the carotid artery. In this paper a model is presented for investigating how the presence of the plaque influences the distribution of the wall shear stress. In complement to a first approach with rigid walls, an FSI model is developed as well to simulate the coupling between the blood flow and the carotid artery deformation. The results show that the presence of the plaque causes an attenuation of the WSS in the after-plaque region as well as the emergence of recirculation areas

Modelling the evolution of cerebral aneurysms: biomechanics, mechanobiology and multiscale modelling

Intracranial aneurysms (IAs) are abnormal dilatations of the cerebral vasculature. Computational modelling may shed light on the aetiology of the disease and lead to improved criteria to assist diagnostic decisions. We briefly review models of aneurysm evolution to date and present a novel fluid-solid-growth (FSG) framework for patient-specific modelling of IA evolution. We illustrate its application to 4 clinical cases depicting an IA. The section of arterial geometry containing the IA is removed and replaced with a cylindrical section: this represents an idealised section of healthy artery upon which IA evolution is simulated. The utilisation of patient-specific geometries enables G&R to be explicitly linked to physiologically realistic spatial distributions and magnitudes of haemodynamic stimuli. In this study, we investigate the hypothesis that elastin degradation is driven by locally low wall shear stress (WSS). In 3 out of 4 cases, the evolved model IA geometry is qualitatively similar to the corresponding in vivo IA geometry. This suggests some tentative support for the hypothesis that low WSS plays a role in the mechanobiology of IA evolution

A structural approach including the behavior of collagen cross-links to model patient-specific human carotid arteries

The final publication is available at Springer via http://dx.doi.org/10.1007/s10439-014-0995-7The objective of this work is to develop a remodeling model for biological matter coupling two different processes in a 3D framework: reorientation of the preferential direction of a given fibered structure and reorientation of the fibrils or filaments that make up such a structure. This work uses the microsphere-based approach to take into account the micro mechanics involved in biological fibered structures regarding both their passive behavior and the reorientation of their micro constituents. Moreover, the macro behavior of the material as a whole is obtained by means of homogenizing the underlying micro response. We associate the orientation space of the integration directions to the physical space of micro-fibrils. To approximate the directional distribution of the fibrils within each fiber bundle, a Bingham probability orientation density function is introduced into the Helmholtz energy function. With all these assumptions, the problem is studied from an energetic point of view, describing the dissipation inherent to remodeling processes, and the evolution equations for both reorientations (change in preferential direction of the network and change in shape of the fibril distribution) re obtained. The model is included in a finite element code which allows computing different geometries and boundary value problems. This results in a complete methodology for characterizing the reorientation evolution of different fibered biological structures, such as cells. Our results show remodeling of fibered structures in two different scales, presenting a qualitatively good agreement with experimental findings in cell mechanics. Hierarchical structures align in the direction of the maximum principal direction of the considered stimulus and narrow in the perpendicular direction. The dissipation rates follows predictable trends although there are no experimental findings to date for comparison. The incorporation of metabolic processes and an insight into cell-oriented mechano-sensing processes can help to overcome the limitations involved.Peer ReviewedPostprint (author's final draft

Physiologic compliance in engineered small-diameter arterial constructs based on an elastomeric substrate.

Compliance mismatch is a significant challenge to long-term patency in small-diameter bypass grafts because it causes intimal hyperplasia and ultimately graft occlusion. Current engineered grafts are typically stiff with high burst pressure but low compliance and low elastin expression. We postulated that engineering small arteries on elastomeric scaffolds under dynamic mechanical stimulation would result in strong and compliant arterial constructs. This study compares properties of engineered arterial constructs based on biodegradable polyester scaffolds composed of either rigid poly(lactide-co-glycolide) (PLGA) or elastomeric poly(glycerol sebacate) (PGS). Adult baboon arterial smooth muscle cells (SMCs) were cultured in vitro for 10 days in tubular, porous scaffolds. Scaffolds were significantly stronger after culture regardless of material, but the elastic modulus of PLGA constructs was an order of magnitude greater than that of porcine carotid arteries and PGS constructs. Deformation was elastic in PGS constructs and carotid arteries but plastic in PLGA constructs. Compliance of arteries and PGS constructs were equivalent at pressures tested. Altering scaffold material from PLGA to PGS significantly decreased collagen content and significantly increased insoluble elastin content in constructs without affecting soluble elastin concentration in the culture medium. PLGA constructs contained no appreciable insoluble elastin. This research demonstrates that: (1) substrate stiffness directly affects in vitro tissue development and mechanical properties; (2) rigid materials likely inhibit elastin incorporation into the extracellular matrix of engineered arterial tissues; and (3) grafts with physiologic compliance and significant elastin content can be engineered in vitro after only days of cell culture

Fibulin-4 is essential for maintaining arterial wall integrity in conduit but not muscular arteries

Homozygous or compound heterozygous mutations in fibulin-4 (FBLN4) lead to autosomal recessive cutis laxa type 1B (ARCL1B), a multisystem disorder characterized by significant cardiovascular abnormalities, including abnormal elastin assembly, arterial tortuosity, and aortic aneurysms. We sought to determine the consequences of a human disease-causing mutation in FBLN4 (E57K) on the cardiovascular system and vascular elastic fibers in a mouse model of ARCL1B. Fbln4E57K/E57K mice were hypertensive and developed arterial elongation, tortuosity, and ascending aortic aneurysms. Smooth muscle cell organization within the arterial wall of large conducting vessels was abnormal, and elastic fibers were fragmented and had a moth-eaten appearance. In contrast, vessel wall structure and elastic fiber integrity were normal in resistance/muscular arteries (renal, mesenteric, and saphenous). Elastin cross-linking and total elastin content were unchanged in large or small arteries, whereas elastic fiber architecture was abnormal in large vessels. While the E57K mutation did not affect Fbln4 mRNA levels, FBLN4 protein was lower in the ascending aorta of mutant animals compared to wild-type arteries but equivalent in mesenteric arteries. We found a differential role of FBLN4 in elastic fiber assembly, where it functions mainly in large conduit arteries. These results suggest that elastin assembly has different requirements depending on vessel type. Normal levels of elastin cross-links in mutant tissue call into question FBLN4\u27s suggested role in mediating lysyl oxidase-elastin interactions. Future studies investigating tissuespecific elastic fiber assembly may lead to novel therapeutic interventions for ARCL1B and other disorders of elastic fiber assembly. 2017 © The Authors, some rights reserved