Time-dependent arterial wall property is an important but difficult topic in vascular mechanics. Hysteresis, which appears during the measurement of arterial pressure-diameter relationship through a cardiac cycle, has been used to indicate time-dependent mechanics of arteries. However, the cause-effect relationship between viscoelastic properties of the arterial wall and hemodynamics, particularly the viscous contribution to hemodynamics, remains challenging. Herein, we show direct comparisons between elastic (loss/storage < 0.1) and highly viscoelastic (loss/storage > 0.45) conduit structures with arterial-like compliance, in terms of their capability of altering pulsatile flow, wall shear and energy level. Conduits were made from varying ratio of vinyl- and methyl-terminated poly(dimethylsiloxane) and were fit in a mimetic circulatory system measuring volumetric flow, pressure, and strain. Results indicated that when compared to elastic conduits, viscoelastic conduits attenuated lumen distension waveforms, producing an average of 11% greater cross-sectional area throughout a mimetic cardiac cycle. In response to such changes in lumen diameter strain, pressure and volumetric flow waves in viscoelastic conduits decreased by 3.9% and 6%, respectively, in the peak-to-peak amplitude. Importantly, the pulsatile waveforms for both diameter strain and volumetric flow demonstrated greater temporal alignment in viscoelastic conduits due to pulsation attenuation, resulting in 25% decrease in the oscillation of wall shear stress. These changes in flow dynamics, due to the viscous component of viscoelastic conduit, could favor arterial health through beneficial influences on cell physiology.

Under the action of the physiological intraocular pressure the human cornea is stressed and reaches a deformed quasi-spherical configuration. If the deformed configuration is known, and the cornea is regarded as a membrane disregarding flexural behaviors, with the static analysis only is possible to estimate the distribution of the average stress across the thickness. In the cornea, the action of the intraocular pressure is supported by collagen fibrils, immersed into an elastin-proteoglycan matrix and organized in a very precise architecture to provide the necessary confinement and transparency to the light. With the goal of understanding the static consequences of shape modifications due to pathological dilatation (ectasia), we present a simplified stress analysis of the human cornea modelled as a membrane. A numerical investigation over 40 patient specific corneas (20 normal, 20 ectatic) is carried out to establish the relationship between the physiological geometry and distribution of the stresses, and to assess the possibility to obtain information on the stress state based only on topographic images. Comparative analyses reveal that, with respect to the normal corneas, in ectatic corneas the pattern of the principal stress lines is modified markedly showing a deviation from the principal orientation of the collagen fibrils. The rotation of the principal stress with respect to the fibril orientation is responsible of the transmission of a large amount of shear stresses onto the elastin-proteoglycan matrix. The anomalous loading of the matrix could be correlated to the evolution of time dependent shape modifications leading to ectasia.

Military personnel sustain head and brain injuries as a result of ballistic, blast, and blunt impact threats. Combat helmets are meant to protect the heads of these personnel during injury events. Studies show peak kinematics and kinetics are attenuated using protective headgear during impacts; however, there is limited experimental biomechanical literature that examines whether or not helmets mitigate peak mechanics delivered to the head and brain during blast. While the mechanical links between blast and brain injury are not universally agreed upon, one hypothesis is that blast energy can be transmitted through the head and into the brain. These transmissions can lead to rapid skull flexure and elevated pressures in the cranial vault, and, therefore, may be relevant in determining injury likelihood. Therefore, it could be argued that assessing a helmet for the ability to mitigate mechanics may be an appropriate paradigm for assessing the potential protective benefits of helmets against blast. In this work, we use a surrogate model of the head and brain to assess whether or not helmets and eye protection can alter mechanical measures during both head-level face-on blast and high forehead blunt impact events. Measurements near the forehead suggest head protection can attenuate brain parenchyma pressures by as much as 49% during blast and 52% during impact, and forces on the inner table of the skull by as much as 80% during blast and 84% during impact, relative to an unprotected head.

Findings from basic science and clinical studies agree that arterial stiffness is fundamental to both the mechanobiology and the biomechanics that dictate vascular health and disease. There is, therefore, an appropriately growing literature on arterial stiffness. Perusal of the literature reveals, however, that many different methods and metrics are used to quantify arterial stiffness, and reported values often differ by orders of magnitude and have different meanings. Without clear definitions and an understanding of possible inter-relations therein, it is increasingly difficult to integrate results from the literature to glean true understanding. In this paper, we briefly review methods that are used to infer values of arterial stiffness that span studies on isolated cells, excised intact vessels, and clinical assessments. We highlight similarities and differences and identify a single theoretical approach that can be used across scales and applications and thus could help to unify future results. We conclude by emphasizing the need to move toward a synthesis of many disparate reports, for only in this way will we be able to move from our current fragmented understanding to a true appreciation of how vascular cells maintain, remodel, or repair the arteries that are fundamental to cardiovascular properties and function.

Trabeculae carneae are irregular structures that cover the endocardial surfaces of both ventricles and account for a significant portion of human ventricular mass. The role of trabeculae carneae in diastolic and systolic functions of the left ventricle (LV) is not well understood. Thus, the objective of this study was to investigate the functional role of trabeculae carneae in the LV. Finite element (FE) analyses of ventricular functions were conducted for three different models of human LV derived from high-resolution magnetic resonance imaging (MRI). The first model comprised trabeculae carneae and papillary muscles, while the second model had papillary muscles and partial trabeculae carneae, and the third model had a smooth endocardial surface. We customized these patient-specific models with myofiber architecture generated with a rule-based algorithm, diastolic material parameters of Fung strain energy function derived from biaxial tests and adjusted with the empirical Klotz relationship, and myocardial contractility constants optimized for average normal ejection fraction (EF) of the human LV. Results showed that the partial trabeculae cutting model had enlarged end-diastolic volume (EDV), reduced wall stiffness, and even increased end-systolic function, indicating that the absence of trabeculae carneae increased the compliance of the LV during diastole, while maintaining systolic function.

Patients who survive a myocardial infarction (MI) are at high risk for ventricular dilation and heart failure. While infarct size is an important determinant of post-MI remodeling, different patients with the same size infarct often display different levels of left ventricular (LV) dilation. The acute physiologic response to MI involves reflex compensation, whereby increases in heart rate (HR), arterial resistance, venoconstriction, and contractility of the surviving myocardium act to maintain mean arterial pressure (MAP). We hypothesized that variability in reflex compensation might underlie some of the reported variability in post-MI remodeling, a hypothesis that is difficult to test using experimental data alone because some reflex responses are difficult or impossible to measure directly. We, therefore, employed a computational model to estimate the balance of compensatory mechanisms from experimentally reported hemodynamic data. We found a strikingly wide range of compensatory reflex profiles in response to MI in dogs and verified that pharmacologic blockade of sympathetic and parasympathetic reflexes nearly abolished this variability. Then, using a previously published model of postinfarction remodeling, we showed that observed variability in compensation translated to variability in predicted LV dilation consistent with published data. Treatment with a vasodilator shifted the compensatory response away from arterial and venous vasoconstriction and toward increased HR and myocardial contractility. Importantly, this shift reduced predicted dilation, a prediction that matched prior experimental studies. Thus, postinfarction reflex compensation could represent both a source of individual variability in the extent of LV remodeling and a target for therapies aimed at reducing that remodeling.

Blood pressure is an important factor both in maintaining body homeostasis and in its disruption. Vascular endothelial cells (ECs) are exposed to varying degrees of blood pressure and therefore play an important role in these physiological and pathological events. However, the effect of blood pressure on EC functions remains to be elucidated. In particular, we do not know how ECs sense and respond to changes in hydrostatic pressure even though the hydrostatic pressure is known to affect the EC functions. Here, we hypothesized that the cellular responses, leading to the reported pressure effects, occur at an early stage of pressure exposure and observed the early-stage dynamics in ECs to elucidate mechanisms through which ECs sense and respond to hydrostatic pressure. We found that exposure to hydrostatic pressure causes an early actomyosin-mediated contraction of ECs without a change in cell morphology. This response could be caused by water efflux from the ECs following exposure to hydrostatic pressure. Although only a limited study, these findings do explain a part of the mechanism through which ECs sense and respond to hydrostatic pressure.

Incompressibility implies that a tissue preserves its volume regardless of the loading conditions. Although this assumption is well-established in arterial wall mechanics, it is assumed to apply for the venous wall without validation. The objective of this study is to test whether the incompressibility assumption holds for the venous wall. To investigate the vascular wall volume under different loading conditions, inflation-extension testing protocol was used in conjunction with intravascular ultrasound (IVUS) in both common iliac arteries (n = 6 swine) and common iliac veins (n = 9 dogs). Use of IVUS allows direct visualizations of lumen dimensions simultaneous with direct measurements of outer dimensions during loading. The arterial tissue was confirmed to preserve volume during various load conditions (p = 0.11) consistent with the literature, while the venous tissue was found to lose volume (about 35%) under loaded conditions (p < 0.05). Using a novel methodology, this study shows the incompressibility assumption does not hold for the venous wall especially at higher pressures, which suggests that there may be fluid loss through the vein wall during loading. This has important implications for coupling of fluid transport across the wall and biomechanics of the wall in healthy and diseased conditions.

A mechanical approach is needed for understanding anorectal function and defecation. Fecal continence is achieved by several interacting mechanisms including anatomical factors, anorectal sensation, rectal compliance, stool consistency, anal muscle strength, motility, and psychological factors. The balance is easily disturbed, resulting in symptoms such as fecal incontinence and constipation. Novel technologies have been developed in recent years for studying anorectal function. Especially, the Fecobionics device, a simulated feces, has gained attention recently. This facilitates new analysis of anorectal mechanical function. In this study, a theoretical model is developed to analyze anorectal mechanophysiological data generated by the Fecobionics device. Theoretical approaches can enhance future interdisciplinary research for unraveling defecatory function, sensory-motor disorders, and symptoms. This is a step in the direction of personalized treatment for gastrointestinal disorders based on optimized subtyping of anorectal disorders.

Pulmonary arterial hypertension (PAH) exerts substantial pressure overload on the right ventricle (RV), inducing RV remodeling and myocardial tissue adaptation often leading to right heart failure. The associated RV free wall (RVFW) adaptation involves myocardial hypertrophy, augmented intrinsic contractility, collagen fibrosis, and structural remodeling in an attempt to cope with pressure overload. If RVFW adaptation cannot maintain the RV stroke volume (SV), RV dilation will prevail as an exit mechanism, which usually decompensates RV function, leading to RV failure. Our knowledge of the factors determining the transition from the upper limit of RVFW adaptation to RV decompensation and the role of fiber remodeling events such as extracellular fibrosis and fiber reorientation in this transition remains very limited. Computational heart models that connect the growth and remodeling (G&R) events at the fiber and tissue levels with alterations in the organ-level function are essential to predict the temporal order and the compensatory level of the underlying mechanisms. In this work, building upon our recently developed rodent heart models (RHM) of PAH, we integrated mathematical models that describe volumetric growth of the RV and structural remodeling of the RVFW. The time-evolution of RV remodeling from control and post-PAH time points was simulated. The results suggest that the augmentation of the intrinsic contractility of myofibers, accompanied by an increase in passive stiffness of RVFW, is among the first remodeling events through which the RV strives to maintain the cardiac output. Interestingly, we found that the observed reorientation of the myofibers toward the longitudinal (apex-to-base) direction was a maladaptive mechanism that impaired the RVFW contractile pattern and advanced along with RV dilation at later stages of PAH. In fact, although individual fibers were more contractile post-PAH, the disruption in the optimal transmural fiber architecture compromised the effective contractile function of the RVFW, contributing to the depressed ejection fraction (EF) of the RV. Our findings clearly demonstrate the critical need for developing multiscale approaches that can model and delineate relationships between pathological alterations in cardiac function and underlying remodeling events across fiber, cellular, and molecular levels.

The impact of left subclavian artery (LSA) coverage during thoracic endovascular aortic repair (TEVAR) on the circulatory system is not fully understood. Here, we coupled a single-phase non-Newtonian model with fluid–structure interaction (FSI) technique to simulate blood flow in an acute type B aortic dissection. Three-element Windkessel model was implemented to reproduce physiological pressure waves, where a new workflow was designed to determine model parameters with the absence of measured data. Simulations were carried out in three geometric models to demonstrate the consequence of TEVAR with the LSA coverage; case A: pre-TEVAR aorta; case B: post-TEVAR aorta with the disappearance of LSA; case C: post-TEVAR aorta with virtually adding LSA. Results show that the blood flow through the compressed true lumen is only 8.43%, which may lead to ischemia in related organs. After TEVAR, the wall pressure on the stented segment increases and blood flow in the supra-aortic branches and true lumen is improved. Meantime, the average deformation of the aorta is obviously reduced due to the implantation of the stent graft. After virtually adding LSA, significant changes in the distribution of blood flow and two indices based on wall shear stress are observed. Moreover, the movement of residual false lumen becomes stable, which could contribute to patient recovery. Overall, this study quantitatively evaluates the efficacy of TEVAR for acute type B aortic dissection and demonstrates that the coverage of LSA has a considerable impact on the important hemodynamic parameters.

The phasic contractions of collecting lymphatic vessels are reduced in strength and occur at diminished frequency when a favorable pressure difference and the resulting antegrade flow create large fluid shear stresses at the luminal surface. This paper describes a minimal phenomenological model of this mechanism that is applied to a previously validated numerical model of a phasically contracting lymphangion. The parameters of the inhibition model are quantitatively matched to observations in isolated segments of rat lymphatic vessel, first for mesenteric lymphatics then for thoracic duct, and outcomes from the numerical model are then qualitatively compared with recent observations in isolated segments of rat thoracic duct.

Mechanical stability analysis is instructive in explaining biological processes like morphogenesis, organogenesis, and pathogenesis of soft tissues. Consideration of the layered, residually stressed structure of tissues, requires accounting for the joint effects of interface conditions and layer incompatibility. This paper is concerned with the influence of imposed rate (incremental) interface conditions (RICs) on critical loads in soft tissues, within the context of linear bifurcation analysis. Aiming at simplicity, we analyze a model of bilayered isotropic hyperelastic (neo-Hookean) spherical shells with residual stresses generated by “shrink-fitting” two perfectly bonded layers with radial interfacial incompatibility. This setting allows a comparison between available, seemingly equivalent, interface conditions commonly used in the literature of layered media stability. We analytically determine the circumstances under which the interface conditions are equivalent or not, and numerically demonstrate significant differences between interface conditions with increasing level of layer incompatibility. Differences of more than tenfold in buckling and 30% in inflation instability critical loads are recorded using the different RICs. Contrasting instability characteristics are also revealed using the different RICs in the presence of incompatibility: inflation instability can occur before pressure maximum, and spontaneous instability may be excluded for thin shells. These findings are relevant to the growing body of stability studies of layered and residually stressed tissues. The impact of interface conditions on critical thresholds is significant in studies that use concepts of instability to draw conclusions about the normal development and the pathologies of tissues like arteries, esophagus, airways, and the brain.

The arteriovenous fistula (AVF) is the main form of vascular access for hemodialysis patients, but its maintenance is very challenging. Its failure is mainly related to intimal hyperplasia (IH), leading to stenosis. The aim of this work was twofold: (i) to perform a computational study for the comparison of the disturbed blood dynamics in different configurations of AVF and (ii) to assess the amount of transition to turbulence developed by the specific geometric configuration of AVF. For this aim, we reconstructed realistic three-dimensional (3D) geometries of two patients with a side-to-end AVF, performing a parametric study by changing the angle of incidence at the anastomosis. We solved the incompressible Navier–Stokes equations modeling the blood as an incompressible and Newtonian fluid. Large eddy simulations (LES) were considered to capture the transition to turbulence developed at the anastomosis. The values of prescribed boundary conditions are obtained from clinical echo-color Doppler (ECD) measurements. To assess the disturbed flow, we considered hemodynamic quantities such as the velocity field, the pressure distribution, and wall shear stresses (WSS) derived quantities, whereas to quantify the transition to turbulence, we computed the standard deviation of the velocity field among different heartbeats and the turbulent kinetic energy.

Current knowledge of traumatic ocular injury is still limited as most studies have focused on the ocular injuries that happened at the anterior part of the eye, whereas the damage to the optic nerve known as traumatic optic neuropathy (TON) is poorly understood. The goal of this study is to understand the mechanism of the TON following the primary blast through a fluid–structure interaction model. An axisymmetric three-dimensional (3D) eye model with detailed orbital components was developed to capture the dynamics of the eye under the blast wave. Our numerical results demonstrated a transient pressure elevation in both vitreous and cerebrospinal fluid (CSF). A high strain rate over 100 s −1 was observed throughout the optic nerve during the blast with the most vulnerable part located at the intracanalicular region. The optic nerve deforming at such a high strain rate may account for the axonal damage and vision loss in patients subjected to the primary blast. The results from this work would enhance the understanding of indirect TON and provide guidance in the design of protective eyewear against such injury.

In this study, a Bayesian optimization based computational framework is developed to investigate the design of transcatheter aortic valve (TAV) leaflets and to optimize leaflet geometry such that its peak stress under the blood pressure of 120 mmHg is reduced. A generic TAV model is parametrized by mathematical equations describing its 2D shape and its 3D stent-leaflet assembly line. Material properties previously obtained for bovine (BP) and porcine pericardium (PP) via a combination of flexural and biaxial tensile testing were incorporated into the finite element (FE) model of TAV. A Bayesian optimization approach was employed to investigate about 1000 leaflet designs for each material under the nominal circular deployment and physiological loading conditions. The optimal parameter values of the TAV model were obtained, corresponding to leaflet shapes that can reduce the peak stress by 16.7% in BP and 18.0% in PP, compared with that from the initial generic TAV model. Furthermore, it was observed that while peak stresses tend to concentrate near the stent-leaflet attachment edge, optimized geometries benefit from more uniform stress distributions in the leaflet circumferential direction. Our analysis also showed that increasing leaflet contact area redistributes peak stresses to the belly region contributing to peak stress reduction. The results from this study may inspire new TAV designs that can have better durability.

Understanding the pressure distributions at the limb-socket interface is essential to the design and evaluation of prosthetic components for lower limb prosthesis users. Force sensing resistors (FSRs) are employed in prosthetics research to measure pressure at this interface due to their low cost, thin profile, and ease of use. While FSRs are known to be sensitive to many sources of error, few studies have systematically quantified these errors using test conditions relevant to lower limb prosthetics. The purpose of this study was to evaluate FSR accuracy for the measurement of lower limb prosthetics interface pressures. Two FSR models (Flexiforce A201 and Interlink 402) were subjected to a series of prosthetic-relevant tests. These tests included: (1) static compression, (2) cyclic compression, and (3) a combined static and cyclic compression protocol mimicking a variable activity (walk–sit–stand) procedure. Flexiforce sensors outperformed Interlink sensors and were then subjected to two additional tests: (4) static curvature and (5) static shear stress. Results demonstrated that FSRs experienced significant errors in all five tests. We concluded that: (1) if used carefully, FSRs can provide an estimate of prosthetic interface pressure, but these measurements should be interpreted within the expected range of possible measurement error given the setup; (2) FSRs should be calibrated in a setup that closely matches how they will be used for taking measurements; and (3) both Flexiforce and Interlink sensors can be used to estimate interface pressures; however, in most cases Flexiforce sensors are likely to provide more accurate measurements.

Virtual Fractional Flow Reserve is an emerging technology employing patient specific Computational Fluid Dynamics simulations to infer the hemodynamic significance of a coronary stenosis. Patient specific boundary conditions are an important aspect of this approach and while most efforts make use of lumped parameter models to capture key phenomena, they lack the ability to specify the associated parameters on a patient specific basis. When applying vFFR in a catheter laboratory setting using X-Ray angiograms as the basis for creating the simulations, there is some indirect functional information available through the observation of the radio-opaque contrast agent motion. In this work, we present a novel method for tuning the lumped parameter arterial resistances, based on simulating the physics of the contrast motion and comparing the observed and simulated arrival times of the contrast front at key points within a coronary tree. We present proof of principle results on a synthetically generated coronary tree comprised of multiple segments, demonstrating that the method can successfully optimise the arterial resistances to reconstruct the underlying velocity and pressure fields, providing a potential new means to improve the patient specificity of simulation-based technologies in this area.

A wide range of emerging therapies from surgical restraint to biomaterial injection to tissue engineering aim to improve heart function and limit adverse remodeling following myocardial infarction (MI). We previously showed that longitudinal surgical reinforcement of large anterior infarcts in dogs could significantly enhance systolic function without restricting diastolic function, but the underlying mechanisms for this improvement are poorly understood. The goal of this study was to construct a finite-element model that could match our previously published data on changes in regional strains and left ventricular function following longitudinal surgical reinforcement, then use the model to explore potential mechanisms for the improvement in systolic function we observed. The model presented here, implemented in FEBio, matches all the key features of our experiments, including diastolic remodeling strains in the ischemic region, small shifts in the end-diastolic pressure-volume relationship (EDPVR), and large changes in the end-systolic pressure-volume relationship (ESPVR) in response to ischemia and to patch application. Detailed examination of model strains and stresses suggests that longitudinal reinforcement reduces peak diastolic fiber stretch and systolic fiber stress in the remote myocardium and shifts those peaks away from the endocardial surface by reshaping the left ventricle (LV). These finding could help guide the development of novel therapies to improve post-MI function by providing specific design objectives.

The blood flow dynamics in a stenosed, subject-specific carotid bifurcation is numerically simulated using Direct Numerical Simulation (DNS) and Reynolds-averaged Navier--Stokes (RANS) equations closed with turbulence models. The former is meant to provide a term of comparison for the RANS calculations, that include classic two-equations models ($k-\epsilon$ and $k-\omega$) as well as a transitional three-equations eddy-viscosity model ($k_T-k_L-\omega$). Pulsatile inlet conditions based on in-vivo ultrasound measurements of blood velocity are used. The blood is modelled as a Newtonian fluid, and the vessel walls are rigid. The main purpose of this work is to highlight the problems related to the use of classic RANS models in the numerical simulation of such flows. The time-averaged DNS results, interpreted in view of their finite-time averaging error, are used to demonstrate the superiority of the transitional RANS model, which is found to provide results closer to DNS than those of conventional models. The transitional model is shown to possess better predictive capabilities in terms of turbulence intensity, temporal evolution of the pressure along the cardiac cycle, and the oscillatory shear index (OSI). Indeed, DNS brings to light the locally transitional or weakly turbulent state of the blood flow, which presents velocity and pressure fluctuations only in the post-stenotic region of the internal carotid artery during systole, while the flow is laminar during diastole.