Role of smooth muscle activation in the static and dynamic mechanical characterization of human aortas.

Experimental data and a suitable material model for human aortas with smooth muscle activation are not available in the literature despite the need for developing advanced grafts; the present study closes this gap. Mechanical characterization of human descending thoracic aortas was performed with and without vascular smooth muscle (VSM) activation. Specimens were taken from 13 heart-beating donors. The aortic segments were cooled in Belzer UW solution during transport and tested within a few hours after explantation. VSM activation was achieved through the use of potassium depolarization and noradrenaline as vasoactive agents. In addition to isometric activation experiments, the quasistatic passive and active stress-strain curves were obtained for circumferential and longitudinal strips of the aortic material. This characterization made it possible to create an original mechanical model of the active aortic material that accurately fits the experimental data. The dynamic mechanical characterization was executed using cyclic strain at different frequencies of physiological interest. An initial prestretch, which corresponded to the physiological conditions, was applied before cyclic loading. Dynamic tests made it possible to identify the differences in the viscoelastic behavior of the passive and active tissue. This work illustrates the importance of VSM activation for the static and dynamic mechanical response of human aortas. Most importantly, this study provides material data and a material model for the development of a future generation of active aortic grafts that mimic natural behavior and help regulate blood pressure.

Review of Systemic Mock Circulation Loops for Evaluation of Implantable Cardiovascular Devices and Biological Tissues.

CLINICAL IMPACT: On needs-based ex vivo monitoring of implantable devices or tissues/organs in cardiovascular simulators provides new insights and paves new paths for device prototypes. The insights gained could not only support the needs of patients, but also inform engineers, scientists and clinicians about undiscovered aspects of diseases (during routine monitoring). We analyze seminal and current work and highlight a variety of opportunities for developing preclinical tools that would improve strategies for future implantable devices. Holistically, mock circulation loop studies can bridge the gap between in vivo and in vitro approaches, as well as clinical and laboratory settings, in a mutually beneficial manner.

Genetic deletion of MMP12 ameliorates cardiometabolic disease by improving insulin sensitivity, systemic inflammation, and atherosclerotic features in mice.

BACKGROUND: Matrix metalloproteinase 12 (MMP12) is a macrophage-secreted protein that is massively upregulated as a pro-inflammatory factor in metabolic and vascular tissues of mice and humans suffering from cardiometabolic diseases (CMDs). However, the molecular mechanisms explaining the contributions of MMP12 to CMDs are still unclear. METHODS: We investigated the impact of MMP12 deficiency on CMDs in a mouse model that mimics human disease by simultaneously developing adipose tissue inflammation, insulin resistance, and atherosclerosis. To this end, we generated and characterized low-density lipoprotein receptor (Ldlr)/Mmp12-double knockout (DKO) mice fed a high-fat sucrose- and cholesterol-enriched diet for 16-20 weeks. RESULTS: DKO mice showed lower cholesterol and plasma glucose concentrations and improved insulin sensitivity compared with LdlrKO mice. Untargeted proteomic analyses of epididymal white adipose tissue revealed that inflammation- and fibrosis-related pathways were downregulated in DKO mice. In addition, genetic deletion of MMP12 led to alterations in immune cell composition and a reduction in plasma monocyte chemoattractant protein-1 in peripheral blood which indicated decreased low-grade systemic inflammation. Aortic en face analyses and staining of aortic valve sections demonstrated reduced atherosclerotic plaque size and collagen content, which was paralleled by an improved relaxation pattern and endothelial function of the aortic rings and more elastic aortic sections in DKO compared to LdlrKO mice. Shotgun proteomics revealed upregulation of anti-inflammatory and atheroprotective markers in the aortas of DKO mice, further supporting our data. In humans, MMP12 serum concentrations were only weakly associated with clinical and laboratory indicators of CMDs. CONCLUSION: We conclude that the genetic deletion of MMP12 ameliorates obesity-induced low-grade inflammation, white adipose tissue dysfunction, biomechanical properties of the aorta, and the development of atherosclerosis. Therefore, therapeutic strategies targeting MMP12 may represent a promising approach to combat CMDs.

Numerical analysis of the impact of cytoskeletal actin filament density alterations onto the diffusive vesicle-mediated cell transport.

The interior of a eukaryotic cell is a highly complex composite material which consists of water, structural scaffoldings, organelles, and various biomolecular solutes. All these components serve as obstacles that impede the motion of vesicles. Hence, it is hypothesized that any alteration of the cytoskeletal network may directly impact or even disrupt the vesicle transport. A disruption of the vesicle-mediated cell transport is thought to contribute to several severe diseases and disorders, such as diabetes, Parkinson's and Alzheimer's disease, emphasizing the clinical relevance. To address the outlined objective, a multiscale finite element model of the diffusive vesicle transport is proposed on the basis of the concept of homogenization, owed to the complexity of the cytoskeletal network. In order to study the microscopic effects of specific nanoscopic actin filament network alterations onto the vesicle transport, a parametrized three-dimensional geometrical model of the actin filament network was generated on the basis of experimentally observed filament densities and network geometries in an adenocarcinomic human alveolar basal epithelial cell. Numerical analyzes of the obtained effective diffusion properties within two-dimensional sampling domains of the whole cell model revealed that the computed homogenized diffusion coefficients can be predicted statistically accurate by a simple two-parameter power law as soon as the inaccessible area fraction, due to the obstacle geometries and the finite size of the vesicles, is known. This relationship, in turn, leads to a massive reduction in computation time and allows to study the impact of a variety of different cytoskeletal alterations onto the vesicle transport. Hence, the numerical simulations predicted a 35% increase in transport time due to a uniformly distributed four-fold increase of the total filament amount. On the other hand, a hypothetically reduced expression of filament cross-linking proteins led to sparser filament networks and, thus, a speed up of the vesicle transport.

Differences in Collagen Fiber Diameter and Waviness between Healthy and Aneurysmal Abdominal Aortas.

Collagen plays a key role in the strength of aortic walls, so studying micro-structural changes during disease development is critical to better understand collagen reorganization. Second-harmonic generation microscopy is used to obtain images of human aortic collagen in both healthy and diseased states. Methods are being developed in order to efficiently determine the waviness, that is, tortuosity and amplitude, as well as the diameter, orientation, and dispersion of collagen fibers, and bundles in healthy and aneurysmal tissues. The results show layer-specific differences in the collagen of healthy tissues, which decrease in samples of aneurysmal aortic walls. In healthy tissues, the thick collagen bundles of the adventitia are characterized by greater waviness, both in the tortuosity and in the amplitude, compared to the relatively thin and straighter collagen fibers of the media. In contrast, most aneurysmal tissues tend to have a more uniform structure of the aortic wall with no significant difference in collagen diameter between the luminal and abluminal layers. An increase in collagen tortuosity compared to the healthy media is also observed in the aneurysmal luminal layer. The data set provided can help improve related material and multiscale models of aortic walls and aneurysm formation.

An active approach of pressure waveform matching for stress-based testing of arteries.

BACKGROUND: Arterial compliance assists the cardiovascular system with three key roles: (i) storing up to 50% of the stroke volume; (ii) ensuring blood flow during diastole; (iii) dampening pressure oscillations through arterial distension. In mock circulation loops (MCLs), arterial compliance was simulated either with membrane, spring, or Windkessel chambers. Although they have been shown to be suitable for cardiac device testing, their passive behavior can limit stress-based testing of arteries. Here we present an active compliance chamber with a feedback control of variable compliance as part of an MCL designed for biomechanical evaluation of arteries under physiological waveforms. MATERIALS AND METHODS: The chamber encloses a piston that changes the volume via a cascaded controller when there is a difference between the real-time pressure and the physiological reference pressure with the aim to equilibrate both pressures. RESULTS: The experimental results showed repeatable physiological waveforms of aortic pressure in health (80-120 mm Hg), systemic hypertension (90-153 mm Hg), and heart failure reduced ejection fraction (78-108 mm Hg). Statistical validation (n = 20) of the function of the chamber is presented against compared raw data. CONCLUSION: We demonstrate that the active compliance chamber can track the actual pressure of the MCL and balance it in real time (every millisecond) with the reference values in order to shape the given pressure waveform. The active compliance chamber is an advanced tool for MCL applications for biomechanical examination of stented arteries and for preclinical evaluation of vascular implants.

Esophagus stretch tests: Biomechanics for tissue engineering and possible implications on the outcome of esophageal atresia repairs performed under excessive tension.

BACKGROUND: Esophageal biomechanical studies are important to understand structural changes resulting from stretches during repair of esophageal atresias as well as to obtain values to compare with the biomechanics of tissue-engineered esophagus in the future. This study aimed to investigate light microscopic changes after uniaxial stretching of the ovine esophagus. METHODS: In vitro uniaxial stretching was performed on esophagi (n = 20) of 1-month-old lambs within 4-6 h post-mortem. Esophagi were divided into 5 groups: control and stretched (1.1, 1.2, 1.3 and 1.4). Force and lengthening were measured with 5 cycles performed on every specimen using a PBS organ bath at 37 °C. Histological studies were performed on the 5 groups. RESULTS: Low forces of ~ 2 N (N) were sufficient for a 1.2-1.25 stretch in the 1st cycle, whereas a three times higher force (~ 6 N) was needed for a stretch of 1.3. In the 2nd to 5th cycle, the tissue weakened and a force of ~ 3 N was sufficient for a stretch of 1.3. Histologically, in the 1.3-1.4 stretch groups, rupture of muscle fibers and capillaries were observed, respectively. Changes in mucosa and collagen fibers could not be observed. CONCLUSIONS: These results offer norm values from the native esophagus to compare with the biomechanics of future tissue-engineered esophagus. Esophageal stretching > 1.3 leads to tears in muscle fibers and to rupture of capillaries. These findings can explain the decrease in microcirculation and scarring in mobilized tissue and possibly offer clues to impaired motility in esophagus atresias repaired under excessive tension.

Role of Vessel Microstructure in the Longevity of End-to-Side Grafts.

Compliance mismatch between the graft and the host artery of an end-to-side (ETS) arterial bypass graft anastomosis increases the intramural stress in the ETS graft-artery junction, and thus may compromise its long-term patency. The present study takes into account the effects of collagen fibers to demonstrate how their orientations alter the stresses. The stresses in an ETS bypass graft anastomosis, as a man-made bifurcation, are compared to those of its natural counterpart with different fiber orientations. Both of the ETS bypass graft anastomosis and its natural counterpart have identical geometric and material models and only their collagen fiber orientations are different. The results indicate that the fiber orientation mismatch between the graft and the host artery may increase the stresses at both the heel and toe regions of the ETS anastomosis (the maximum principal stress at the heel and toe regions increased by 72% and 12%, respectively). Our observations, thus, propose that the mismatch between the collagen fiber orientations of the graft and the host artery, independent of the effect of the suture line, may induce aberrant stresses to the anastomosis of the bypass graft.

An efficient and accurate method for modeling nonlinear fractional viscoelastic biomaterials.

Computational biomechanics plays an important role in biomedical engineering: using modeling to understand pathophysiology, treatment and device design. While experimental evidence indicates that the mechanical response of most tissues is viscoelastic, current biomechanical models in the computational community often assume hyperelastic material models. Fractional viscoelastic constitutive models have been successfully used in literature to capture viscoelastic material response; however, the translation of these models into computational platforms remains limited. Many experimentally derived viscoelastic constitutive models are not suitable for three-dimensional simulations. Furthermore, the use of fractional derivatives can be computationally prohibitive, with a number of current numerical approximations having a computational cost that is 𝒪 ( N T 2 ) and a storage cost that is 𝒪(NT ) (NT denotes the number of time steps). In this paper, we present a novel numerical approximation to the Caputo derivative which exploits a recurrence relation similar to those used to discretize classic temporal derivatives, giving a computational cost that is 𝒪(NT ) and a storage cost that is fixed over time. The approximation is optimized for numerical applications, and an error estimate is presented to demonstrate the efficacy of the method. The method, integrated into a finite element solid mechanics framework, is shown to be unconditionally stable in the linear viscoelastic case. It was then integrated into a computational biomechanical framework, with several numerical examples verifying the accuracy and computational efficiency of the method, including in an analytic test, in an analytic fractional differential equation, as well as in a computational biomechanical model problem.

Biomechanical relevance of the microstructure in artery walls with a focus on passive and active components.

The microstructure of arteries, consisting, in particular, of collagen, elastin, and vascular smooth muscle cells, plays a very significant role in their biomechanical response during a cardiac cycle. In this article, we highlight the microstructure and the contributions of each of its components to the overall mechanical behavior. We also describe the changes of the microstructure that occur as a result of abdominal aortic aneurysms and disease, such as atherosclerosis. We also focus on how the passive and active constituents are incorporated into a mathematical model without going into detail of the mathematical formulation. We conclude by mentioning open problems toward a better characterization of the biomechanical aspects of arteries that will be beneficial for a better understanding of cardiovascular pathophysiology.

Compressibility and Anisotropy of the Ventricular Myocardium: Experimental Analysis and Microstructural Modeling.

While the anisotropic behavior of the complex composite myocardial tissue has been well characterized in recent years, the compressibility of the tissue has not been rigorously investigated to date. In the first part of this study, we present experimental evidence that passive-excised porcine myocardium exhibits volume change. Under tensile loading of a cylindrical specimen, a volume change of 4.1±1.95% is observed at a peak stretch of 1.3. Confined compression experiments also demonstrate significant volume change in the tissue (loading applied up to a volumetric strain of 10%). In order to simulate the multiaxial passive behavior of the myocardium, a nonlinear volumetric hyperelastic component is combined with the well-established Holzapfel-Ogden anisotropic hyperelastic component for myocardium fibers. This framework is shown to describe the experimentally observed behavior of porcine and human tissues under shear and biaxial loading conditions. In the second part of the study, a representative volumetric element (RVE) of myocardium tissue is constructed to parse the contribution of the tissue vasculature to observed volume change under confined compression loading. Simulations of the myocardium microstructure suggest that the vasculature cannot fully account for the experimentally measured volume change. Additionally, the RVE is subjected to six modes of shear loading to investigate the influence of microscale fiber alignment and dispersion on tissue-scale mechanical behavior.

Perspectives on Sharing Models and Related Resources in Computational Biomechanics Research.

The role of computational modeling for biomechanics research and related clinical care will be increasingly prominent. The biomechanics community has been developing computational models routinely for exploration of the mechanics and mechanobiology of diverse biological structures. As a result, a large array of models, data, and discipline-specific simulation software has emerged to support endeavors in computational biomechanics. Sharing computational models and related data and simulation software has first become a utilitarian interest, and now, it is a necessity. Exchange of models, in support of knowledge exchange provided by scholarly publishing, has important implications. Specifically, model sharing can facilitate assessment of reproducibility in computational biomechanics and can provide an opportunity for repurposing and reuse, and a venue for medical training. The community's desire to investigate biological and biomechanical phenomena crossing multiple systems, scales, and physical domains, also motivates sharing of modeling resources as blending of models developed by domain experts will be a required step for comprehensive simulation studies as well as the enhancement of their rigor and reproducibility. The goal of this paper is to understand current perspectives in the biomechanics community for the sharing of computational models and related resources. Opinions on opportunities, challenges, and pathways to model sharing, particularly as part of the scholarly publishing workflow, were sought. A group of journal editors and a handful of investigators active in computational biomechanics were approached to collect short opinion pieces as a part of a larger effort of the IEEE EMBS Computational Biology and the Physiome Technical Committee to address model reproducibility through publications. A synthesis of these opinion pieces indicates that the community recognizes the necessity and usefulness of model sharing. There is a strong will to facilitate model sharing, and there are corresponding initiatives by the scientific journals. Outside the publishing enterprise, infrastructure to facilitate model sharing in biomechanics exists, and simulation software developers are interested in accommodating the community's needs for sharing of modeling resources. Encouragement for the use of standardized markups, concerns related to quality assurance, acknowledgement of increased burden, and importance of stewardship of resources are noted. In the short-term, it is advisable that the community builds upon recent strategies and experiments with new pathways for continued demonstration of model sharing, its promotion, and its utility. Nonetheless, the need for a long-term strategy to unify approaches in sharing computational models and related resources is acknowledged. Development of a sustainable platform supported by a culture of open model sharing will likely evolve through continued and inclusive discussions bringing all stakeholders at the table, e.g., by possibly establishing a consortium.

Numerical aspects of anisotropic failure in soft biological tissues favor energy-based criteria: A rate-dependent anisotropic crack phase-field model.

A deeper understanding to predict fracture in soft biological tissues is of crucial importance to better guide and improve medical monitoring, planning of surgical interventions and risk assessment of diseases such as aortic dissection, aneurysms, atherosclerosis and tears in tendons and ligaments. In our previous contribution (Gültekin et al., 2016) we have addressed the rupture of aortic tissue by applying a holistic geometrical approach to fracture, namely the crack phase-field approach emanating from variational fracture mechanics and gradient damage theories. In the present study, the crack phase-field model is extended to capture anisotropic fracture using an anisotropic volume-specific crack surface function. In addition, the model is equipped with a rate-dependent formulation of the phase-field evolution. The continuum framework captures anisotropy, is thermodynamically consistent and based on finite strains. The resulting Euler-Lagrange equations are solved by an operator-splitting algorithm on the temporal side which is ensued by a Galerkin-type weak formulation on the spatial side. On the constitutive level, an invariant-based anisotropic material model accommodates the nonlinear elastic response of both the ground matrix and the collagenous components. Subsequently, the basis of extant anisotropic failure criteria are presented with an emphasis on energy-based, Tsai-Wu, Hill, and principal stress criteria. The predictions of the various failure criteria on the crack initiation, and the related crack propagation are studied using representative numerical examples, i.e. a homogeneous problem subjected to uniaxial and planar biaxial deformations is established to demonstrate the corresponding failure surfaces whereas uniaxial extension and peel tests of an anisotropic (hypothetical) tissue deal with the crack propagation with reference to the mentioned failure criteria. Results favor the energy-based criterion as a better candidate to reflect a stable and physically meaningful crack growth, particularly in complex three-dimensional geometries with a highly anisotropic texture at finite strains.

Multiscale and Multiaxial Mechanics of Vascular Smooth Muscle.

Mathematical models can facilitate an integrative understanding of the complexity underlying biological structure and function, but they must be informed and validated by empirical data. Uniaxial contraction of an arterial ring is a well-used in vitro approach for studying characteristics of smooth muscle contractility even though this experimental arrangement does not mimic the in vivo vascular geometry or loading. In contrast, biaxial contraction of an inflated and axially extended excised vessel provides broader information, both passive and active, under more realistic conditions. Few investigations have compared these two in vitro approaches directly, namely how their results overlap, how they differ, or if each provides unique complementary information. Toward this end, we present, to our knowledge, a new multiscale mathematical model of arterial contractility accounting for structural and functional constituents at molecular, cellular, and tissue levels. The artery is assumed to be a thick-walled incompressible cylinder described by an anisotropic model of the extracellular matrix and, to our knowledge, novel model of smooth muscle contractility. The latter includes a 3D structural sensitivity to deformation, including microscale muscle filament overlap and filament lattice spacing. The overall model captures uniaxial and biaxial experimental contraction data, which was not possible when accounting for filament overlap alone. The model also enables parameter sensitivity studies, which confirmed that uniaxial contraction tests are not as efficient as biaxial tests for identifying changes in vascular smooth muscle function.

Length adaptation of smooth muscle contractile filaments in response to sustained activation.

Airway and bladder smooth muscles are known to undergo length adaptation under sustained contraction. This adaptation process entails a remodelling of the intracellular actin and myosin filaments which shifts the peak of the active force-length curve towards the current length. Smooth muscles are therefore able to generate the maximum force over a wide range of lengths. In contrast, length adaptation of vascular smooth muscle has attracted very little attention and only a handful of studies have been reported. Although their results are conflicting on the existence of a length adaptation process in vascular smooth muscle, it seems that, at least, peripheral arteries and arterioles undergo such adaptation. This is of interest since peripheral vessels are responsible for pressure regulation, and a length adaptation will affect the function of the cardiovascular system. It has, e.g., been suggested that the inward remodelling of resistance vessels associated with hypertension disorders may be related to smooth muscle adaptation. In this study we develop a continuum mechanical model for vascular smooth muscle length adaptation by assuming that the muscle cells remodel the actomyosin network such that the peak of the active stress-stretch curve is shifted towards the operating point. The model is specialised to hamster cheek pouch arterioles and the simulated response to stepwise length changes under contraction. The results show that the model is able to recover the salient features of length adaptation reported in the literature.

A phase-field approach to model fracture of arterial walls: Theory and finite element analysis.

This study uses a recently developed phase-field approach to model fracture of arterial walls with an emphasis on aortic tissues. We start by deriving the regularized crack surface to overcome complexities inherent in sharp crack discontinuities, thereby relaxing the acute crack surface topology into a diffusive one. In fact, the regularized crack surface possesses the property of Gamma-Convergence, i.e. the sharp crack topology is restored with a vanishing length-scale parameter. Next, we deal with the continuous formulation of the variational principle for the multi-field problem manifested through the deformation map and the crack phase-field at finite strains which leads to the Euler-Lagrange equations of the coupled problem. In particular, the coupled balance equations derived render the evolution of the crack phase-field and the balance of linear momentum. As an important aspect of the continuum formulation we consider an invariant-based anisotropic constitutive model which is additively decomposed into an isotropic part for the ground matrix and an exponential anisotropic part for the two families of collagen fibers embedded in the ground matrix. In addition we propose a novel energy-based anisotropic failure criterion which regulates the evolution of the crack phase-field. The coupled problem is solved using a one-pass operator-splitting algorithm composed of a mechanical predictor step (solved for the frozen crack phase-field parameter) and a crack evolution step (solved for the frozen deformation map); a history field governed by the failure criterion is successively updated. Subsequently, a conventional Galerkin procedure leads to the weak forms of the governing differential equations for the physical problem. Accordingly, we provide the discrete residual vectors and a corresponding linearization yields the element matrices for the two sub-problems. Finally, we demonstrate the numerical performance of the crack phase-field model by simulating uniaxial extension and simple shear fracture tests performed on specimens obtained from a human aneurysmatic thoracic aorta. Model parameters are obtained by fitting the set of novel experimental data to the predicted model response; the finite element results agree favorably with the experimental findings.

A thick-walled fluid-solid-growth model of abdominal aortic aneurysm evolution: application to a patient-specific geometry.

We propose a novel thick-walled fluid-solid-growth (FSG) computational framework for modeling vascular disease evolution. The arterial wall is modeled as a thick-walled nonlinearly elastic cylindrical tube consisting of two layers corresponding to the media-intima and adventitia, where each layer is treated as a fiber-reinforced material with the fibers corresponding to the collagenous component. Blood is modeled as a Newtonian fluid with constant density and viscosity; no slip and no-flux conditions are applied at the arterial wall. Disease progression is simulated by growth and remodeling (G&R) of the load bearing constituents of the wall. Adaptions of the natural reference configurations and mass densities of constituents are driven by deviations of mechanical stimuli from homeostatic levels. We apply the novel framework to model abdominal aortic aneurysm (AAA) evolution. Elastin degradation is initially prescribed to create a perturbation to the geometry which results in a local decrease in wall shear stress (WSS). Subsequent degradation of elastin is driven by low WSS and an aneurysm evolves as the elastin degrades and the collagen adapts. The influence of transmural G&R of constituents on the aneurysm development is analyzed. We observe that elastin and collagen strains evolve to be transmurally heterogeneous and this may facilitate the development of tortuosity. This multiphysics framework provides the basis for exploring the influence of transmural metabolic activity on the progression of vascular disease.

Investigating the role of smooth muscle cells in large elastic arteries: a finite element analysis.

Physiological loading in large elastic arteries is considered to be mainly carried by the passive components of the media but it is not known how much the contraction of the smooth muscle cells is actually involved in the load carrying. Smooth muscle contraction is considered to occur in a relatively slow time domain but the contraction is able to produce significant tension. In the present work the role of smooth muscle contraction in large elastic arteries is investigated by analyzing how changes in the intracellular calcium, and thereby the active tone of smooth muscle cells, influence the deformation and stress behavior; different intracellular calcium functions and medial wall thicknesses with cycling internal pressure are studied. In particular, a recently proposed mechanochemical model (Murtada et al., 2012. J. Theor. Biol. 297, 176-186), which links intracellular calcium with mechanical contraction and an anisotropic model representing the elastin/collagen composite, was implemented into a 3D finite element framework. Details of the implementation procedure are described and a verification of the model implementation is provided by means of the isometric contraction/relaxation analysis of a medial strip at optimal muscle length. In addition, numerically obtained pressure-radius relationships of arterial rings modeled with one and two layers are analyzed with different geometries and at different calcium levels; a comparison with the Laplace equation is provided. Finally, a two-layer arterial ring is loaded with a realistic pressure wave and with various intracellular calcium functions (different amplitudes and mean values) and medial wall thicknesses; residual stresses are considered. The finite element results show that changes in the calcium amplitudes hardly have an influence on the current inner ring radius and the circumferential stress. However, an increase in the mean intracellular calcium value and the medial wall thickness leads to a clear influence on the deformation and the stress behavior.

Cell adhesion affects the properties of interstitial fluid flow: A study using multiscale poroelastic composite modeling.

In this study, we conduct a multiscale, multiphysics modeling of the brain gray matter as a poroelastic composite. We develop a customized representative volume element based on cytoarchitectural features that encompass important microscopic components of the tissue, namely the extracellular space, the capillaries, the pericapillary space, the interstitial fluid, cell-cell and cell-capillary junctions, and neuronal and glial cell bodies. Using asymptotic homogenization and direct numerical simulation, the effective properties at the tissue level are identified based on microscopic properties. To analyze the influence of various microscopic elements on the effective/macroscopic properties and tissue response, we perform sensitivity analyses on cell junction (cluster) stiffness, cell junction diameter (dimensions), and pericapillary space width. The results of this study suggest that changes in cell adhesion can greatly affect both mechanical and hydraulic (interstitial fluid flow and porosity) features of brain tissue, consistent with the effects of neurodegenerative diseases.

Multimodal experimental studies of the passive mechanical behavior of human aortas: Current approaches and future directions.

Cardiovascular diseases are the leading cause of death worldwide and include, among others, critical conditions of the aortic wall. Importantly, such critical conditions require effective diagnosis and treatment, which are not yet accurate enough. However, they could be significantly strengthened with predictive material models of the aortic wall. In particular, such predictive models could support surgical decisions, preoperative planning, and estimation of postoperative tissue remodeling. However, developing a predictive model requires experimental data showing both structural parameters and mechanical behavior. Such experimental data can be obtained using multimodal experiments. This review therefore discusses the current approaches to multimodal experiments. Importantly, the strength of the aortic wall is determined primarily by its passive components, i.e., mainly collagen, elastin, and proteoglycans. Therefore, this review focuses on multimodal experiments that relate the passive mechanical behavior of the human aortic wall to the structure and organization of its passive components. In particular, the multimodal experiments are classified according to the expected results. Multiple examples are provided for each experimental class and summarized with highlighted advantages and disadvantages of the method. Finally, future directions of multimodal experiments are envisioned and evaluated. STATEMENT OF SIGNIFICANCE: Multimodal experiments are innovative approaches that have gained interest very quickly, but also recently. This review presents therefore a first clear summary of groundbreaking research in the field of multimodal experiments. The benefits and limitations of various types of multimodal experiments are thoroughly discussed, and a comprehensive overview of possible results is provided. Although this review focuses on multimodal experiments performed on human aortic tissues, the methods used and described are not limited to human aortic tissues but can be extended to other soft materials.