Biomechanics and Modeling in Mechanobiology

Correction to: Prediction of femoral strength using 3D finite element models reconstructed from DXA images: validation against experiments In the original publication of the article, Fig. 3 and Tables 2, 4 and 5 were published with errors. The issue was caused by an error in the code used to predict femoral strength in the finite element (FE) models.

A data-driven model to study utero-ovarian blood flow physiology during pregnancy Abstract In this paper, we describe a mathematical model of the cardiovascular system in human pregnancy. An automated, closed-loop 1D–0D modelling framework was developed, and we demonstrate its efficacy in (1) reproducing measured multi-variate cardiovascular variables (pulse pressure, total peripheral resistance and cardiac output) and (2) providing automated estimates of variables that have not been measured (uterine arterial and venous blood flow, pulse wave velocity, pulsatility index). This is the first model capable of estimating volumetric blood flow to the uterus via the utero-ovarian communicating arteries. It is also the first model capable of capturing wave propagation phenomena in the utero-ovarian circulation, which are important for the accurate estimation of arterial stiffness in contemporary obstetric practice. The model will provide a basis for future studies aiming to elucidate the physiological mechanisms underlying the dynamic properties (changing shapes) of vascular flow waveforms that are observed with advancing gestation. This in turn will facilitate the development of methods for the earlier detection of pathologies that have an influence on vascular structure and behaviour.

The combined impact of tissue heterogeneity and fixed charge for models of cartilage: the one-dimensional biphasic swelling model revisited Abstract Articular cartilage is a complex, anisotropic, stratified tissue with remarkable resilience and mechanical properties. It has been subject to extensive modelling as a multiphase medium, with many recent studies examining the impact of increasing detail in the representation of this tissue’s fine scale structure. However, further investigation of simple models with minimal constitutive relations can nonetheless inform our understanding at the foundations of soft tissue simulation. Here, we focus on the impact of heterogeneity with regard to the volume fractions of solid and fluid within the cartilage. Once swelling pressure due to cartilage fixed charge is also present, we demonstrate that the multiphase modelling framework is substantially more complicated, and thus investigate this complexity, especially in the simple setting of a confined compression experiment. Our findings highlight the importance of locally, and thus heterogeneously, approaching pore compaction for load bearing in cartilage models, while emphasising that such effects can be represented by simple constitutive relations. In addition, simulation predictions are observed for the sensitivity of stress and displacement in the cartilage to variations in the initial state of the cartilage and thus the details of experimental protocol, once the tissue is heterogeneous. These findings are for the simplest models given only heterogeneity in volume fractions and swelling pressure, further emphasising that the complex behaviours associated with the interaction of volume fraction heterogeneity and swelling pressure are likely to persist for simulations of cartilage representations with more fine-grained structural detail of the tissue.

Crack propagation in cortical bone is affected by the characteristics of the cement line: a parameter study using an XFEM interface damage model Abstract Bulk properties of cortical bone have been well characterized experimentally, and potent toughening mechanisms, e.g., crack deflections, have been identified at the microscale. However, it is currently difficult to experimentally measure local damage properties and isolate their effect on the tissue fracture resistance. Instead, computer models can be used to analyze the impact of local characteristics and structures, but material parameters required in computer models are not well established. The aim of this study was therefore to identify the material parameters that are important for crack propagation in cortical bone and to elucidate what parameters need to be better defined experimentally. A comprehensive material parameter study was performed using an XFEM interface damage model in 2D to simulate crack propagation around an osteon at the microscale. The importance of 14 factors (material parameters) on four different outcome criteria (maximum force, fracture energy, crack length and crack trajectory) was evaluated using ANOVA for three different osteon orientations. The results identified factors related to the cement line to influence the crack propagation, where the interface strength was important for the ability to deflect cracks. Crack deflection was also favored by low interface stiffness. However, the cement line properties are not well determined experimentally and need to be better characterized. The matrix and osteon stiffness had no or low impact on the crack pattern. Furthermore, the results illustrated how reduced matrix toughness promoted crack penetration of the cement line. This effect is highly relevant for the understanding of the influence of aging on crack propagation and fracture resistance in cortical bone.

Direct and inverse identification of constitutive parameters from the structure of soft tissues. Part 2: dispersed arrangement of collagen fibers Abstract This paper investigates on the relationship between the arrangement of collagen fibers within soft tissues and parameters of constitutive models. Starting from numerical experiments based on biaxial loading conditions, the study addresses both the direct (from structure to mechanics) and the inverse (from mechanics to structure) problems, solved introducing optimization problems for model calibration and regression analysis. A campaign of parametric analyses is conducted in order to consider fibers distributions with different main orientation and angular dispersion. Different anisotropic constitutive models are employed, accounting for fibers dispersion either with a generalized structural approach or with an increasing number of strain energy terms. Benchmark data sets, toward which constitutive models are fitted, are built by employing a multiscale description of fiber nonlinearities and accounting for fibers dispersion with an angular integration method. Results show how the optimal values of constitutive parameters obtained from model calibration vary as a function of fibers arrangement and testing protocol. Moreover, the fitting capabilities of constitutive models are discussed. A novel strategy for model calibration is also proposed, in order to obtain a robust accuracy with respect to different loading conditions starting from a low number of mechanical tests. Furthermore, novel results useful for the inverse determination of the mean angle and the variance of fibers distribution are obtained. Therefore, the study contributes: to better design procedures for model calibration; to account for mechanical alterations due to remodeling mechanisms; and to gain structural information in a nondestructive way.

Shear stress in the microvasculature: influence of red blood cell morphology and endothelial wall undulation Abstract The effect of red blood cells and the undulation of the endothelium on the shear stress in the microvasculature is studied numerically using the lattice Boltzmann–immersed boundary method. The results demonstrate a significant effect of both the undulation of the endothelium and red blood cells on wall shear stress. Our results also reveal that morphological alterations of red blood cells, as occur in certain pathologies, can significantly affect the values of wall shear stress. The resulting fluctuations in wall shear stress greatly exceed the nominal values, emphasizing the importance of the particulate nature of blood as well as a more realistic description of vessel wall geometry in the study of hemodynamic forces. We find that within the channel widths investigated, which correspond to those found in the microvasculature, the inverse minimum distance normalized to the channel width between the red blood cell and the wall is predictive of the maximum wall shear stress observed in straight channels with a flowing red blood cell. We find that the maximum wall shear stress varies several factors more over a range of capillary numbers (dimensionless number relating strength of flow to membrane elasticity) and reduced areas (measure of deflation of the red blood cell) than the minimum wall shear stress. We see that waviness reduces variation in minimum and maximum shear stresses among different capillary and reduced areas.

Experimental study of muscle permeability under various loading conditions Abstract The permeability of a few muscle tissues under various loading conditions is characterized. To this end, we develop an experimental apparatus for permeability measurements which is based on the falling head method. We also design a dedicated sample holder which directs the flow through the tissue and simultaneously enables to pre-compress it. Although outside of the scope of this work, we recall that the permeability of the muscle has a crucial role in the pathophysiology of various diseases such as the compartment syndrome. Following the measurements of porcine, beef, chicken and lamb samples, we find that the permeability decreases with the pre-compression of the tissue. Similar decrease is observed following dehydration of the tissue. Remarkably, we find that within a physiological pressure range the permeabilities of the various samples are quite similar. This suggests that the muscle permeability is governed by a common micro-mechanical mechanism in which the blood propagates through the interstitial spaces. Under physiological loading conditions, the muscle permeability is in the range between 80 and 230 \({\frac{{\text {mm}}^{4}}{{\text{N s}}}}\) .

A CFD-based Kriging surrogate modeling approach for predicting device-specific hemolysis power law coefficients in blood-contacting medical devices Abstract Most stress-based hemolysis models used in computational fluid dynamics (CFD) are based on an empirical power law correlation between hemolysis generation and the flow-induced stress and exposure time. Empirical model coefficients are typically determined by fitting global hemolysis measurements in simplified blood shearing devices under uniform shear conditions and with well-defined exposure times. CFD simulations using these idealized global empirical coefficients are then performed to predict hemolysis in a medical device with complex hemodynamics. The applicability, however, of this traditional approach of using idealized coefficients for a real device with varying exposure times and non-uniform shear is currently unknown. In this study, we propose a new approach for determining device- and species-specific hemolysis power law coefficients (C, a, and b). The approach consists of calculating multiple hemolysis solutions using different sets of coefficients to map the hemolysis response field in three-dimensional (C, a, b) parameter space. The resultant response field is then compared with experimental data in the same device to determine the coefficients that when incorporated into the locally defined power law model yield correct global hemolysis predictions. We first develop the generalized approach by deriving analytical solutions for simple uniform and non-uniform shear flows (planar Couette flow and circular Poiseuille flow, respectively) that allow us to continuously map the hemolysis solution in (C, a, b) parameter space. We then extend our approach to more practical cases relevant to blood-contacting medical devices by replacing the requirement for an analytical solution in our generalized approach with CFD and Kriging surrogate modeling. Finally, we apply our verified CFD-based Kriging surrogate modeling approach to predict the device- and species-specific power law coefficients for developing laminar flow in a small capillary tube. We show that the resultant coefficients are much different than traditional idealized coefficients obtained from simplified uniform shear experiments and that using such idealized coefficients yields a highly inaccurate prediction of hemolysis that is in error by more than 2000% compared to experiments. Our approach and surrogate modeling framework may be applied to more complex medical devices and readily extended to determine empirical coefficients for other continuum-based models of hemolysis and other forms of flow-induced blood damage (e.g., platelet activation and thrombosis).

Transient active force generation and stress fibre remodelling in cells under cyclic loading Abstract The active cytoskeleton is known to play an important mechanistic role in cellular structure, spreading, and contractility. Contractility is actively generated by stress fibres (SF), which continuously remodel in response to physiological dynamic loading conditions. The influence of actin-myosin cross-bridge cycling on SF remodelling under dynamic loading conditions has not previously been uncovered. In this study, a novel SF cross-bridge cycling model is developed to predict transient active force generation in cells subjected to dynamic loading. Rates of formation of cross-bridges within SFs are governed by the chemical potentials of attached and unattached myosin heads. This transient cross-bridge cycling model is coupled with a thermodynamically motivated framework for SF remodelling to analyse the influence of transient force generation on cytoskeletal evolution. A 1D implementation of the model is shown to correctly predict complex patterns of active cell force generation under a range of dynamic loading conditions, as reported in previous experimental studies.

On the compressibility and poroelasticity of human and murine skin Abstract A total of 37 human and 33 murine skin samples were subjected to uniaxial monotonic, cyclic, and relaxation experiments. Detailed analysis of the three-dimensional kinematic response showed that skin volume is significantly reduced as a consequence of a tensile elongation. This behavior is most pronounced in monotonic but persists in cyclic tests. The dehydration associated with volume loss depends on the osmolarity of the environment, so that tension relaxation changes as a consequence of modifying the ionic strength of the environmental bath. Similar to ex vivo observations, complementary in vivo stretching experiments on human volar forearms showed strong in-plane lateral contraction. A biphasic homogenized model is proposed which allows representing all relevant features of the observed mechanical response.