Biomechanics and Modeling in Mechanobiology最新文献

Due to the anatomical complexity of the aortic arch for the development of stent-grafts for total repair, this region remains without a validated and routinely used endovascular option. In this work, a modular stent-graft for aneurysms that covers all aortic arch zones, proposed by us and previously structurally evaluated, was evaluated from the point of view of haemodynamics using fluid-structural numerical simulations. Blood was assumed to be non-Newtonian shear-thinning using the Carreau model, and the arterial wall was assumed to be anisotropic hyperelastic using the Holzapfel model. Nitinol and expanded polytetrafluoroethylene (PTFE-e) were used as materials for the stents and the graft, respectively. Nitinol was modelled as a superelastic material with shape memory by the Auricchio model, and PTFE-e was modelled as an isotropic linear elastic material. To validate the numerical model, a silicone model representative of the aneurysmal aorta was subjected to tests on an experimental bench representative of the circulatory system. The numerical results showed that the stent-graft restored flow behaviour, making it less oscillatory, but increasing the strain rate, turbulence kinetic energy, and viscosity compared to the pathological case. Taking the mean of the entire cycle, the increase in turbulence kinetic energy was 198.82% in the brachiocephalic trunk, 144.63% in the left common carotid artery and 284.03% in the left subclavian artery after stent-graft implantation. Based on wall shear stress parameters, it was possible to identify that the internal branches of the stent-graft and the stent-graft fixation sites in the artery were the most favourable regions for the deposition and accumulation of thrombus. In these regions, the oscillating shear index reached the maximum value of 0.5 and the time-averaged wall shear stress was close to zero, which led the relative residence time to reach values above 15 Pa⁻¹. The stent-graft was able to preserve flow in the supra-aortic branches.

During the Ross procedure, an aortic heart valve is replaced by a patient’s own pulmonary valve. The pulmonary autograft subsequently undergoes substantial growth and remodeling (G&R) due to its exposure to increased hemodynamic loads. In this study, we developed a homogenized constrained mixture model to understand the observed adaptation of the autograft leaflets in response to the changed hemodynamic environment. This model was based on the hypothesis that tissue G&R aims to preserve mechanical homeostasis for each tissue constituent. To model the Ross procedure, we simulated the exposure of a pulmonary valve to aortic pressure conditions and the subsequent G&R of the valve. Specifically, we investigated the effects of assuming either stress- or stretch-based mechanical homeostasis, the use of blood pressure control, and the effect of root dilation. With this model, we could explain different observations from published clinical studies, such as the increase in thickness, change in collagen organization, and change in tissue composition. In addition, we found that G&R based on stress-based homeostasis could better capture the observed changes in tissue composition than G&R based on stretch-based homeostasis, and that root dilation or blood pressure control can result in more leaflet elongation. Finally, our model demonstrated that successful adaptation can only occur when the mechanically induced tissue deposition is sufficiently larger than tissue degradation, such that leaflet thickening overrules leaflet dilation. In conclusion, our findings demonstrated that G&R based on mechanical homeostasis can capture the observed heart valve adaptation after the Ross procedure. Finally, this study presents a novel homogenized mixture model that can be used to investigate other cases of heart valve G&R as well.

Despite significant research efforts in the continuum modeling of biological growth, certain aspects have been overlooked. For instance, numerous investigations have examined the influence of morphogenetic cell behaviors, like division and intercalation, on the mechanical response of passive (non-growing) tissues. Yet, their impact on active growth dynamics remains inadequately explored. A key reason for this inadequacy stems from challenges in the continuum treatment of cell-level processes. While some coarse-grained models have been proposed to address these shortcomings, a focus on cell division and cell expansion has been missing, rendering them unusable when it comes to modeling growth. Moreover, existing studies are limited to two-dimensional tissues and are yet to be formally extended to three-dimensional multicellular systems. To address these limitations, we here present a generalized multiscale model for three-dimensional aggregates that accounts for complex morphogenetic movements that include division, expansion, and intercalation. The proposed continuum theory thus allows for a comprehensive exploration into the growth and dissipation mechanics of proliferating aggregates, such as spheroids and organoids.

In this study, we present a computational framework designed to evaluate virtual scenarios of cardiac resynchronization therapy (CRT) and compare their effectiveness based on relevant clinical biomarkers. Our approach involves electro-mechanical numerical simulations personalized, for patients with left bundle branch block, by means of a calibration obtained using data from Electro-Anatomical Mapping System (EAMS) measures acquired by cardiologists during the CRT procedure, as well as ventricular pressures and volumes, both obtained pre-implantation. We validate the calibration by using EAMS data coming from right pacing conditions. Three patients with fibrosis and three without are considered to explore various conditions. Our virtual scenarios consist of personalized numerical experiments, incorporating different positions of the left electrode along reconstructed epicardial veins; different locations of the right electrode; different ventriculo-ventricular delays. The aim is to offer a comprehensive tool capable of optimizing CRT efficiency for individual patients. We provide preliminary answers on optimal electrode placement and delay, by computing some relevant biomarkers such as (dP/dt_{max}), ejection fraction, stroke work. From our numerical experiments, we found that the latest activated segment during sinus rhythm is an effective choice for the non-fibrotic cases for the location of the left electrode. Also, our results showed that the activation of the right electrode before the left one seems to improve the CRT performance for the non-fibrotic cases. Last, we found that the CRT performance seems to improve by positioning the right electrode halfway between the base and the apex. This work is on the line of computational works for the study of CRT and introduces new features in the field, such as the presence of the epicardial veins and the movement of the right electrode. All these studies from the different research groups can in future synergistically flow together in the development of a tool which clinicians could use during the procedure to have quantitative information about the patient’s propagation in different scenarios.

Endovascular coil embolization is one of the primary treatment techniques for cerebral aneurysms. Although it is a well-established and minimally invasive method, it bears the risk of suboptimal coil placement which can lead to incomplete occlusion of the aneurysm possibly causing recurrence. One of the key features of coils is that they have an imprinted natural shape supporting the fixation within the aneurysm. For the spatial discretization, our mathematical coil model is based on the discrete elastic rod model which results in a dimension-reduced 1D system of differential equations. We include bending and twisting responses to account for the coils natural curvature and allow for the placement of several coils having different material parameters. Collisions between coil segments and the aneurysm wall are handled by an efficient contact algorithm that relies on an octree based collision detection. In time, we use a standard symplectic semi-implicit Euler time stepping method. Our model can be easily incorporated into blood flow simulations of embolized aneurysms. In order to differentiate optimal from suboptimal placements, we employ a suitable in silico Raymond–Roy-type occlusion classification and measure the local packing density in the aneurysm at its neck, wall region and core. We investigate the impact of uncertainties in the coil parameters and embolization procedure. To this end, we vary the position and the angle of insertion of the micro-catheter, and approximate the local packing density distributions by evaluating sample statistics.

We characterized the tensile behavior of sclera, optic nerve (ON), and ON sheath in eyes from donors with glaucoma, for comparison with published data without glaucoma. Twelve freshly harvested eyes were obtained from donors with history of glaucoma, of average age 86 ± 7 (standard deviation) years. Rectangular samples were taken from anterior, equatorial, posterior, and peripapillary sclera, and ON sheath, while ON was in native form and measured using calipers. Under physiological temperature and humidity, tissues were preconditioned at 5% strain before loading at 0.1 mm/s. Force–displacement data were converted into engineering stress–strain curves fit by reduced polynomial hyperelastic models and analyzed by tangent moduli at 3% and 7% strain. Data were compared with an age-matched sample of 7 published control eyes. Optic atrophy was supported by significant reduction in ON cross section to 73% of normal in glaucomatous eyes. Glaucomatous was significantly stiffer than control in equatorial and peripapillary regions (P < 0.001). However, glaucomatous ON and sheath were significantly less stiff than control, particularly at low strain (P < 0.001). Hyperelastic models were well fit to stress–strain data (R² > 0.997). Tangent moduli had variability similar to control in most regions, but was abnormally large in peripapillary sclera. Tensile properties were varied independently among various regions of the same eyes. Glaucomatous sclera is abnormally stiff, but the ON and sheath are abnormally compliant. These abnormalities correspond to properties predicted by finite element analysis to transfer potentially pathologic stress to the vulnerable disk and lamina cribrosa region during adduction eye movement.

Acute myocardial infarction (MI) leads to a loss of cardiac function which, following adverse ventricular remodeling (AVR), can ultimately result in heart failure. Tissue-engineered contractile patches placed over the infarct offer potential for restoring cardiac function and reducing AVR. In this computational study, we investigate how improvement of pump function depends on the orientation of the cardiac patch and the fibers therein relative to the left ventricle (LV). Additionally, we examine how model outcome depends on the choice of material properties for healthy and infarct tissue. In a finite element model of LV mechanics, an infarction was induced by eliminating active stress generation and increasing passive tissue stiffness in a region comprising 15% of the LV wall volume. The cardiac patch was modeled as a rectangular piece of healthy myocardium with a volume of 25% of the infarcted tissue. The orientation of the patch was varied from 0 to (150^ circ ) relative to the circumferential plane. The infarct reduced stroke work by 34% compared to the healthy heart. Optimal patch support was achieved when the patch was oriented parallel to the subepicardial fiber direction, restoring 9% of lost functionality. Typically, about one-third of the total recovery was attributed to the patch, while the remainder resulted from restored functionality in native myocardium adjacent to the infarct. The patch contributes to cardiac function through two mechanisms. A contribution of tissue in the patch and an increased contribution of native tissue, due to favorable changes in mechanical boundary conditions.

Although tissue stiffness is known to play an important role in aortic dilatation, the current guidelines for offering preventative surgery in patients with Marfan syndrome rely solely on the aortic diameter. In this systematic review and meta-analysis, we analyze and compare literature on in vivo aortic stiffness measures in Marfan patients. Our aim is to assess the potential of these measurements as early indicators of aortic dilatation. Following the PRISMA guidelines, we collected literature on diameter and three in vivo stiffness measures: Pulse wave velocity (PWV), (beta )-stiffness index (SI) and distensibility, at five different aortic locations in patients with Marfan syndrome. Results were reviewed and compared against each other. For meta-analysis, an augmented dataset was created by combining data from the literature. Regression with respect to age and statistical comparisons were performed. Thirty articles reporting data from 1925 patients with Marfan and 836 patients without Marfan were reviewed. PWV was found to be higher in Marfan, but only in dilated aortas. Distensibility was found to be lower even in non-dilated aortas, and its decrease was associated with higher chances of developing aortic dilatation. (beta )-SI was higher in Marfan patients and was positively correlated with the rate of aortic dilatation, emphasizing its role as a valuable indicator. In our meta-analysis, all stiffness measures showed a significant variation with age. Distensibility and (beta )-stiffness index were different in Marfan patients at all locations, and the difference was more pronounced after accounting for age-related variation. From the literature, (beta )-SI and distensibility emerge as the best predictors of future aortic dilatation. Our meta-analysis quantifies age-related changes in aortic stiffness and highlights the importance of accounting for age in comparing these measurements. Missing diameter values in the literature limited our analysis. Further investigation of criteria combining stiffness and diameter is recommended to better assist clinical decisions for prophylactic surgery.

Pulmonary hypertension (PH) is a debilitating disease that alters the structure and function of both the proximal and distal pulmonary vasculature. This alters pressure-flow relationships in the pulmonary arterial and venous trees, though there is a critical knowledge gap in the relationships between proximal and distal hemodynamics in disease. Multiscale computational models enable simulations in both the proximal and distal vasculature. However, model inputs and measured data are inherently uncertain, requiring a full analysis of the sensitivity and uncertainty of the model. Thus, this study quantifies model sensitivity and output uncertainty in a spatially multiscale, pulse-wave propagation model of pulmonary hemodynamics. The model includes fifteen proximal arteries and twelve proximal veins, connected by a two-sided, structured tree model of the distal vasculature. We use polynomial chaos expansions to expedite sensitivity and uncertainty quantification analyses and provide results for both the proximal and distal vasculature. We quantify uncertainty in blood pressure, blood flow rate, wave intensity, wall shear stress, and cyclic stretch. The latter two are important stimuli for endothelial cell mechanotransduction. We conclude that, while nearly all the parameters in our system have some influence on model predictions, the parameters describing the density of the microvascular beds have the largest effects on all simulated quantities in both the proximal and distal arterial and venous circulations.