Sara Roccabianca

A Microstructurally Motivated Model of Arterial Wall Mechanics with Mechanobiological Implications

Through mechanobiological control of the extracellular matrix, and hence local stiffness, smooth muscle cells of the media and fibroblasts of the adventitia play important roles in arterial homeostasis, including adaptations to altered hemodynamics, injury, and disease. We present a new approach to model arterial wall mechanics that seeks to define better the mechanical environments of the media and adventitia while avoiding the common prescription of a traction-free reference configuration. Specifically, we employ the concept of constituent-specific deposition stretches from the growth and remodeling literature and define a homeostatic state at physiologic pressure and axial stretch that serves as a convenient biologically and clinically relevant reference configuration. Information from histology and multiphoton imaging is then used to prescribe structurally motivated constitutive relations for a bi-layered model of the wall. The utility of this approach is demonstrated by describing in vitro measured biaxial pressure–diameter and axial force–length responses of murine carotid arteries and predicting the associated intact and radially cut traction-free configurations. The latter provides a unique validation while confirming that this constrained mixture approach naturally recovers estimates of residual stresses, which are fundamental to wall mechanics, without the usual need to prescribe an opening angle that is only defined conveniently on cylindrical geometries and cannot be measured in vivo. Among other findings, the model suggests that medial and adventitial stresses can be nearly uniform at physiologic loads, albeit at separate levels, and that the adventitia bears increasingly more load at supra-physiologic pressures while protecting the media from excessive stresses.

Quantification of regional differences in aortic stiffness in the aging human

There has been a growing awareness over the past decade that stiffening of the aorta, and its attendant effects on hemodynamics, is both an indicator and initiator of diverse cardiovascular, neurovascular, and renovascular diseases. Although different clinical metrics of arterial stiffness have been proposed and found useful in particular situations, there remains a need to understand better the complex interactions between evolving aortic stiffness and the hemodynamics. Computational fluid-solid-interaction (FSI) models are amongst the most promising means to understand such interactions for one can parametrically examine effects of regional variations in material properties and arterial geometry on local and systemic blood pressure and flow. Such models will not only increase our understanding, they will also serve as important steps towards the development of fluid-solid-growth (FSG) models that can further examine interactions between the evolving wall mechanics and hemodynamics that lead to arterial adaptations or disease progression over long periods. In this paper, we present a consistent quantification and comparison of regional nonlinear biaxial mechanical properties of the human aorta based on 19 data sets available in the literature and we calculate associated values of linearized stiffness over the cardiac cycle that are useful for initial large-scale FSI and FSG simulations. It is shown, however, that there is considerable variability amongst the available data and consequently that there is a pressing need for more standardized biaxial testing of the human aorta to collect data as a function of both location and age, particularly for young healthy individuals who serve as essential controls.

Controlling Bandgap in Electroactive Polymer-Based Structures

A waveguide with a periodic structure is able to filter waves whose frequencies lie in the band-gap ranges displayed in dispersion diagrams. The lengths of these forbidden bands depend on the contrast in material and geometrical properties of parts of the system which realize the periodicity. In this paper, a novel way to control band gaps is proposed: to set the geometric characteristics of a prestretched waveguide made of soft dielectric elastomer applying an external voltage to pairs of electrodes applied with a regular pattern on the device. The technique proves to be feasible and is able to tune accurately the position of band gaps over all frequency spectrum. For the investigated system, a device able to guide flexural waves, bandgap ranges of about 100-200 Hz have been obtained over frequencies on the order of 1 kHz.

Biomechanical roles of medial pooling of glycosaminoglycans in thoracic aortic dissection

Spontaneous dissection of the human thoracic aorta is responsible for significant morbidity and mortality, yet this devastating biomechanical failure process remains poorly understood. In this paper, we present finite element simulations that support a new hypothesis for the initiation of aortic dissections that is motivated by extensive histopathological observations. Specifically, our parametric simulations show that the pooling of glycosaminoglycans/proteoglycans that is singularly characteristic of the compromised thoracic aorta in aneurysms and dissections can lead to significant stress concentrations and intra-lamellar Donnan swelling pressures. We submit that these localized increases in intramural stress may be sufficient both to disrupt the normal cell-matrix interactions that are fundamental to aortic homeostasis and to delaminate the layered microstructure of the aortic wall and thereby initiate dissection. Hence, pathologic pooling of glycosaminoglycans/proteoglycans within the medial layer of the thoracic aortic should be considered as a possible target for clinical intervention.

Computational modelling suggests good, bad and ugly roles of glycosaminoglycans in arterial wall mechanics and mechanobiology.

The medial layer of large arteries contains aggregates of the glycosaminoglycan hyaluronan and the proteoglycan versican. It is increasingly thought that these aggregates play important mechanical and mechanobiological roles despite constituting only a small fraction of the normal arterial wall. In this paper, we offer a new hypothesis that normal aggregates of hyaluronan and versican pressurize the intralamellar spaces, and thereby put into tension the radial elastic fibres that connect the smooth muscle cells to the elastic laminae, which would facilitate mechanosensing. This hypothesis is supported by novel computational simulations using two complementary models, a mechanistically based finite-element mixture model and a phenomenologically motivated continuum hyperelastic model. That is, the simulations suggest that normal aggregates of glycosaminoglycans/proteoglycans within the arterial media may play equally important roles in supporting (i.e. a structural role) and sensing (i.e. an instructional role) mechanical loads. Additional simulations suggest further, however, that abnormal increases in these aggregates, either distributed or localized, may over-pressurize the intralamellar units. We submit that these situations could lead to compromised mechanosensing, anoikis and/or reduced structural integrity, each of which represent fundamental aspects of arterial pathologies seen, for example, in hypertension, ageing and thoracic aortic aneurysms and dissections.

Effects of age-associated regional changes in aortic stiffness on human hemodynamics revealed by computational modeling

Although considered by many as the gold standard clinical measure of arterial stiffness, carotid-to-femoral pulse wave velocity (cf-PWV) averages material and geometric properties over a large portion of the central arterial tree. Given that such properties may evolve differentially as a function of region in cases of hypertension and aging, among other conditions, there is a need to evaluate the potential utility of cf-PWV as an early diagnostic of progressive vascular stiffening. In this paper, we introduce a data-driven fluid-solid-interaction computational model of the human aorta to simulate effects of aging-related changes in regional wall properties (e.g., biaxial material stiffness and wall thickness) and conduit geometry (e.g., vessel caliber, length, and tortuosity) on several metrics of arterial stiffness, including distensibility, augmented pulse pressure, and cyclic changes in stored elastic energy. Using the best available biomechanical data, our results for PWV compare well to findings reported for large population studies while rendering a higher resolution description of evolving local and global metrics of aortic stiffening. Our results reveal similar spatio-temporal trends between stiffness and its surrogate metrics, except PWV, thus indicating a complex dependency of the latter on geometry. Lastly, our analysis highlights the importance of the tethering exerted by external tissues, which was iteratively estimated until hemodynamic simulations recovered typical values of tissue properties, pulse pressure, and PWV for each age group.

Local Versus Global Mechanical Effects of Intramural Swelling in Carotid Arteries

Glycosaminoglycans (GAGs) are increasingly thought to play important roles in arterial mechanics and mechanobiology. We recently suggested that these highly negatively charged molecules, well known for their important contributions to cartilage mechanics, can pressurize intralamellar units in elastic arteries via a localized swelling process and thereby impact both smooth muscle mechanosensing and structural integrity. In this paper, we report osmotic loading experiments on murine common carotid arteries that revealed different degrees and extents of transmural swelling. Overall geometry changed significantly with exposure to hypo-osmotic solutions, as expected, yet mean pressure-outer diameter behaviors remained largely the same. Histological analyses revealed further that the swelling was not always distributed uniformly despite being confined primarily to the media. This unexpected finding guided a theoretical study of effects of different distributions of swelling on the wall stress. Results suggested that intramural swelling can introduce highly localized changes in the wall mechanics that could induce differential mechanobiological responses across the wall. There is, therefore, a need to focus on local, not global, mechanics when examining issues such as swelling-induced mechanosensing.

BIFURCATION OF ELASTIC MULTILAYERS

The occurrence of a bifurcation during loading of a multilayer sets a limit on structural deformability, and therefore represents an important factor in the design of composites. Since bifurcation is strongly influenced by the contact conditions at the interfaces between the layers, mechanical modelling of these is crucial. The theory of incremental bifurcation is reviewed for elastic multilayers, when these are subject to a finite strain before bifurcation, corresponding to uniform tension/compression and finite bending. The interlaminar contact is described by introducing linear imperfect interfaces. Results are critically discussed in view of applications and available experiments. 5.

Understanding the mechanics of the bladder through experiments and theoretical models: Where we started and where we are heading

Bladder control problems affect both men and women and range from an overactive bladder, to urinary incontinence, to bladder obstruction and cancer. These disorders affect more than 200 million people worldwide. Loss of bladder function significantly affects the quality of life, both physically and psychologically, and also has a large impact on the healthcare system, i.e., the incurring costs related to diagnosis, treatment and medical/nursing care. Improvements in diagnostic capabilities and disease management are essential to improve patient care and quality of life and reduce the economic burden associated with bladder disorders. This paper summarizes some of the key contributions to understanding the mechanics of the bladder ranging from work conducted in the 1970s through the present time with a focus on material testing and theoretical modeling. Advancements have been made in these areas and a significant contribution to these changes was related to technological improvements.

Comparison of tensile strength and time to closure between an intermittent aberdeen suture pattern and conventional methods of closure for the body wall of dogs

OBJECTIVE To compare tensile strength and time to completion of body wall closure among 3 suture patterns. SAMPLE Eighteen 5 × 5-cm leather specimens and sixty-eight 5 × 5-cm full-thickness tissue specimens from the ventral portion of the abdominal body wall of 17 canine cadavers. PROCEDURES During experiment 1 of a 2-experiment study, each leather specimen was cut in half and sutured with a simple interrupted or simple continuous pattern or continuous pattern with intermittent Aberdeen knots (intermittent Aberdeen pattern). During experiment 2, 4 tissue specimens were obtained from each cadaver; the linea alba of 3 specimens was incised and closed with 1 of the 3 suture patterns evaluated in experiment 1, and the fourth specimen was left intact as a control. All leather and tissue specimens underwent mechanical testing. Time to completion, mode of failure, and maximum force at failure (Fmax) were compared among the suture patterns. RESULTS In experiment 1, the mean Fmax for the simple continuous and intermittent Aberdeen patterns was significantly greater than that for the simple interrupted pattern. In experiment 2, the mean Fmax for specimens obtained cranial to the umbilicus was greater than that for specimens obtained caudal to the umbilicus, and the mean time to completion for both continuous suture patterns was significantly less than that for the simple interrupted pattern. Most (34/51) sutured tissue specimens failed because the suture cut through the tissue at the suture-tissue interface. CONCLUSIONS AND CLINICAL RELEVANCE Results indicated that the intermittent Aberdeen pattern may be an alternative for body wall closure in dogs.