Sur le remodelage des tissus osseux anisotropesOn the remodelling of anisotropic bone tissue

Growth (change of relaxed lengths) and remodelling (change of mechanical properties) are both involved in the morphogenesis of biological tissues. To model them is of paramount import for progressing both in scientific understanding and health technologies. We model bone tissue as a microstructured continuum, whose mechanical properties at the macroscopic scale are described by a linear, anisotropic elastic response that evolves in time. Our kinematics is rich enough to allow for the microstructural evolution, as well as for the interplay between stress, growth and remodelling. This is a unified approach to the mechanics of growth and remodelling, in which all balance laws derive from one virtual-power principle. As a first application, we study the problem of stiffness remodelling due to planar rotation of the microstructure, excluding bulk growth and all physiological response to mechanical stimuli (passive remodelling). To cite this article: A. DiCarlo et al., C. R. Mecanique 334 (2006).     

Multi-scale modelling of textile reinforced artificial tubular aortic heart valves

Tissue engineered heart valves equivalent to the native aortic heart valves are in development as an alternative to available prostheses. To achieve sufficient mechanical stiffness for application in tissue engineered valves exposed to the systemic circulation, the tissue is reinforced by a textile scaffold. Mechanical testing of structurally different textiles used as reinforcement in tissue engineered heart valves is expensive and time-consuming. The current study seeks to predict the behaviour of textile reinforced artificial heart valves using a multi-scale modelling approach. The complex textile structure was divided into simplified models at different scales. Virtual experiments were conducted on each of these models and their response was fitted by appropriate isotropic and anisotropic hyperelastic material models. The textile response was then used in a macro heart valve model, which was subjected to dynamic cardiac loading. It was shown that the current modelling approach is in good agreement with the real valve behaviour.     

A single strain-based growth law predicts concentric and eccentric cardiac growth during pressure and volume overload

Adult cardiac muscle adapts to mechanical changes in the environment by growth and remodeling (G&R) via a variety of mechanisms. Hypertrophy develops when the heart is subjected to chronic mechanical overload. In ventricular pressure overload (e.g. due to aortic stenosis) the heart typically reacts by concentric hypertrophic growth, characterized by wall thickening due to myocyte radial growth when sarcomeres are added in parallel. In ventricular volume overload, an increase in filling pressure (e.g. due to mitral regurgitation) leads to eccentric hypertrophy as myocytes grow axially by adding sarcomeres in series leading to ventricular cavity enlargement that is typically accompanied by some wall thickening. The specific biomechanical stimuli that stimulate different modes of ventricular hypertrophy are still poorly understood. In a recent study, based on in vitro studies in micropatterned myocyte cell cultures subjected to stretch, we proposed that cardiac myocytes grow longer to maintain a preferred sarcomere length in response to increased fiber strain and grow thicker to maintain interfilament lattice spacing in response to increased cross-fiber strain. Here, we test whether this growth law is able to predict concentric and eccentric hypertrophy in response to aortic stenosis and mitral valve regurgitation, respectively, in a computational model of the adult canine heart coupled to a closed loop model of circulatory hemodynamics. A non-linear finite element model of the beating canine ventricles coupled to the circulation was used. After inducing valve alterations, the ventricles were allowed to adapt in shape in response to mechanical stimuli over time. The proposed growth law was able to reproduce major acute and chronic physiological responses (structural and functional) when integrated with comprehensive models of the pressure-overloaded and volume-overloaded canine heart, coupled to a closed-loop circulation. We conclude that strain-based biomechanical stimuli can drive cardiac growth, including wall thickening during pressure overload.     

A generic approach towards finite growth with examples of athlete's heart, cardiac dilation, and cardiac wall thickening

The objective of this work is to establish a generic continuum-based computational concept for finite growth of living biological tissues. The underlying idea is the introduction of an incompatible growth configuration which naturally introduces a multiplicative decomposition of the deformation gradient into an elastic and a growth part. The two major challenges of finite growth are the kinematic characterization of the growth tensor and the identification of mechanical driving forces for its evolution. Motivated by morphological changes in cell geometry, we illustrate a micromechanically motivated ansatz for the growth tensor for cardiac tissue that can capture both strain-driven ventricular dilation and stress-driven wall thickening. Guided by clinical observations, we explore three distinct pathophysiological cases: athlete's heart, cardiac dilation, and cardiac wall thickening. We demonstrate the computational solution of finite growth within a fully implicit incremental iterative Newton-Raphson based finite element solution scheme. The features of the proposed approach are illustrated and compared for the three different growth pathologies in terms of a generic bi-ventricular heart model.     

Effects of atrial fibrillation on the arterial fluid dynamics: a modelling perspective

Atrial fibrillation (AF) is the most common form of arrhythmia with accelerated and irregular heart rate (HR), leading to both heart failure and stroke and being responsible for an increase in cardiovascular morbidity and mortality. In spite of its importance, the direct effects of AF on the arterial hemodynamic patterns are not completely known to date. Based on a multiscale modelling approach, the proposed work investigates the effects of AF on the local arterial fluid dynamics. AF and normal sinus rhythm (NSR) conditions are simulated extracting 2000 \({\mathrm {RR}}\) heartbeats and comparing the most relevant cardiac and vascular parameters at the same HR (75 bpm). Present outcomes evidence that the arterial system is not able to completely absorb the AF-induced variability, which can be even amplified towards the peripheral circulation. AF is also able to locally alter the wave dynamics, by modifying the interplay between forward and backward signals. The sole heart rhythm variation (i.e., from NSR to AF) promotes an alteration of the regular dynamics at the arterial level which, in terms of pressure and peripheral perfusion, suggests a modification of the physiological phenomena ruled by periodicity (e.g., regular organ perfusion) and a possible vascular dysfunction due to the prolonged exposure to irregular and extreme values. The present study represents a first modeling approach to characterize the variability of arterial hemodynamics in presence of AF, which surely deserves further clinical investigation.     

Dynamic principle for interaction between heart and arterial system

Various steady models for interaction between heart and arterial system have been given in literature. In our recent study, a dynamic principle, i.e. the principle of least cardiac work is proposed, and a dynamic model for interaction of heart and arterial system is established. Preliminary results of our experiments show that both the principle and the model are consistent with the physiological phenomena. It reveals that the present analysis may offer a new measure for the study of dynamic process of interaction between heart and arterial system.     

Growth and remodeling of the left ventricle: A case study of myocardial infarction and surgical ventricular restoration

Cardiac growth and remodeling in the form of chamber dilation and wall thinning are typical hallmarks of infarct-induced heart failure. Over time, the infarct region stiffens, the remaining muscle takes over function, and the chamber weakens and dilates. Current therapies seek to attenuate these effects by removing the infarct region or by providing structural support to the ventricular wall. However, the underlying mechanisms of these therapies are unclear, and the results remain suboptimal. Here we show that myocardial infarction induces pronounced regional and transmural variations in cardiac form. We introduce a mechanistic growth model capable of predicting structural alterations in response to mechanical overload. Under a uniform loading, this model predicts non-uniform growth. Using this model, we simulate growth in a patient-specific left ventricle. We compare two cases, growth in an infarcted heart, pre-operative, and growth in the same heart, after the infarct was surgically excluded, post-operative. Our results suggest that removing the infarct and creating a left ventricle with homogeneous mechanical properties does not necessarily reduce the driving forces for growth and remodeling. These preliminary findings agree conceptually with clinical observations.     

A continuum mechanics framework and a constitutive model for remodelling of collagen gels and collagenous tissues

Collagen is a very important protein of the human body and is responsible for the structural stability of many body components. Furthermore, collagen fibre networks are able to grow and remodel themselves, which enables them to adjust to varying physiological conditions. This remodelling is accomplished by fibre-producing cells, such as fibroblasts. The ability to adjust to new physiological conditions is very important, for example in wound healing. In the present paper, a theoretical framework for modelling collagenous tissues and collagen gels is proposed. Continuum mechanics is employed to describe the kinematics of the collagen, and affine deformations of fibres are assumed. Biological soft tissues can be approximated as being hyperelastic, and the constitutive model for the collagen fabric is therefore formulated in terms of a strain energy function. This strain energy function includes a density function that describes the distribution of the collagen fibre orientation. The density function evolves according to an evolution law, where fibres tend to reorient towards the direction of maximum Cauchy stress. The remodelling of the collagen network is also assumed to include a pre-stretching of collagen fibres, accomplished by fibroblasts. The theoretical framework is applied to experiments performed on collagen gels, where gels were exposed to remodelling under both biaxial and uniaxial constraints. The proposed model was able to predict both the resulting collagen distribution and the resulting stress-strain relationships obtained for the remodelled collagen gels. The influence of the most important model parameters is demonstrated, and it appears that there is a fairly unique set of model parameters that gives an optimal fit to the experimental data.     

Modeling Heart Development

Mechanics plays a major role in heart development. This paper reviews some of the mechanical aspects involved in theoretical modeling of the embryonic heart as it transforms from a single tube into a four-chambered pump. In particular, large deformations and significant alterations in structure lead to highly nonlinear boundary value problems. First, the biological background for the problem is discussed. Next, a modified elasticity theory is presented that includes active contraction and growth, and the theory is incorporated into a finite element analysis. Finally, models for the heart are presented to illustrate the developmental processes of growth, remodeling, and morphogenesis. Combining such models with appropriate experiments should shed light on the complex mechanisms involved in cardiac development. This revised version was published online in July 2006 with corrections to the Cover Date.     

PHCA实验中犬心脏的非线性动力学研究

按照非线性理论,实施了犬的深低温停循环（Profound Hypothermia and Circulatory Arrest,简称PHCA）实验,并应用混沌理论对实验中采集的心电信号进行了研究,得出以下结论：（1）混沌特征参数可反映心脏的总体动态特征,并可作为心血管疾病早期诊断的依据。（2）在正常的生理状态下心脏的运动是混沌的,而在病理状态下则趋于有序。     

计算机模拟在胚胎形态发育机理研究中的最新进展及前景

近几年来，基于有限元的计算机模拟在生物力学，尤其是在胚胎形态学中的应用所取得的成果，大大加深了人们对于胚胎形态发育过程的认识．本文通过介绍几例计算机模拟在心脏、原肠胚和神经胚形成过程以及细胞力学研究中的应用成果，阐述计算机模拟在胚胎学中的应用现状和前景     

A Comparison of Phenomenologic Growth Laws for Myocardial Hypertrophy

The heart grows in response to changes in hemodynamic loading during normal development and in response to valve disease, hypertension, and other pathologies. In general, a left ventricle subjected to increased afterload (pressure overloading) exhibits concentric growth characterized by thickening of individual myocytes and the heart wall, while one experiencing increased preload (volume overloading) exhibits eccentric growth characterized by lengthening of myocytes and dilation of the cavity. Predictive models of cardiac growth could be important tools in evaluating treatments, guiding clinical decision making, and designing novel therapies for a range of diseases. Thus, in the past 20 years there has been considerable effort to simulate growth within the left ventricle. While a number of published equations or systems of equations (often termed “growth laws”) can capture some aspects of experimentally observed growth patterns, no direct comparisons of the various published models have been performed. Here we examine eight of these laws and compare them in a simple test-bed in which we imposed stretches measured during in vivo pressure and volume overload. Laws were compared based on their ability to predict experimentally measured patterns of growth in the myocardial fiber and radial directions as well as the ratio of fiber-to-radial growth. Three of the eight laws were able to reproduce most key aspects of growth following both pressure and volume overload. Although these three growth laws utilized different approaches to predict hypertrophy, they all employed multiple inputs that were weakly correlated during in vivo overload and therefore provided independent information about mechanics.     

Gravitational effects on global hemodynamics in different postures: A closed-loop multiscale mathematical analysis

We present a novel methodology and strategy to predict pressures and flow rates in the global cardio-vascular network in different postures varying from supine to upright. A closed-loop, multiscale mathematical model of the entire cardiovascular system (CVS) is developed through an integration of one-dimensional (1D) modeling of the large systemic arteries and veins, and zero-dimensional (0D) lumped-parameter modeling of the heart, the cardiac-pulmonary circulation, the cardiac and venous valves, as well as the microcirculation. A versatile junction model is proposed and incorporated into the 1D model to cope with splitting and/or merging flows across a multibranched junc-tion, which is validated to be capable of estimating both subcritical and supercritical flows while ensuring the mass conservation and total pressure continuity. To model grav-itational effects on global hemodynamics during postural change, a robust venous valve model is further established for the 1D venous flows and distributed throughout the entire venous network with consideration of its anatomically real-istic numbers and locations. The present integrated model is proven to enable reasonable prediction of pressure and flow rate waveforms associated with cardiopulmonary circu-lation, systemic circulation in arteries and veins, as well as microcirculation within normal physiological ranges, partic-ularly in mean venous pressures, which well match the in vivo measurements. Applications of the cardiovascular model at different postures demonstrate that gravity exerts remarkable influence on arterial and venous pressures, venous returns and cardiac outputs whereas venous pressures below the heart level show a specific correlation between central venous and hydrostatic pressures in right atrium and veins.     

An energy-based crack growth criterion for modelling elastic–plastic ductile fracture

A crack growth criterion is derived based on the Griffith energy concept and the cohesive zone model for modelling fracture in elastic–plastic ductile materials. The criterion is implemented in the finite element context by a virtual crack extension technique. An automatic modelling of the ductile fracture process is realised by combining a local remeshing procedure and the criterion. The validity of the derived criterion is examined by modelling a compact tension specimen.     

考虑载荷特性的骨重建力学调控机制

骨组织具有适应变化力学环境的能力.通过分析骨组织适应力学环境的调控机制,吸纳工程强度设计准则思想,提出考虑载荷特性的骨重建力学调控机制,探讨载荷特性对力学激励的影响,对牙槽骨“张力区骨增生和压力区骨吸收”的现象进行分析和数值模拟.结果表明考虑载荷特性的骨重建力学调控机制是合理的,是骨重建力学调控机制理论的补充和完善.     

Damage-Bone Remodelling Theory: An Extension to Anisotropic Damage

Everyday activities damage bone, and this damage is normally repaired in a continuous remodelling process. When an imbalance in this remodelling process occurs, bones may become more susceptible to fracture. This paper is concerned with a derivation of: (a) the general rule for bone remodelling in interaction with anisotropic damage and (b) the associated thermodynamic restrictions. The procedure of Coleman and Noll, utilizing the Clausius–Duhem inequality is used and is provided as basis for a consistent formulation of bone remodelling involving a chemical reaction and mass transfer between two constituents in presence of microcracks. It is hoped that this work provides a rational basis for the practical use of such theoretical results.     

基于实验的心肌被动力本构模型

在狗心脏外科手术和心肌力学性能试验的基础上,对心肌力学性能实验数据进行处理和拟合,并应用有限元方法对心肌的单拉实验、松弛实验进行数值模拟和计算. 得到不同心肌位点的本构模型的非线性弹性和黏性参数,从而发展了心肌被动力的非线性黏弹性本构模型,体现了心脏力学行为的非均匀性和黏弹性. 在理论模型和试验数据的基础上,开发了有限元软件ABAQUS的VUMAT材料子程序,应用于数值心脏的仿真研究.      

Flow physics of normal and abnormal bioprosthetic aortic valves

Flow physics of transvalvular flows in the aorta with bioprosthetic valves are investigated using computational modelling. For the efficient simulations of flow-structure-interaction in transvalvular flows, a simplified, reduced degree of freedom valve model is employed with a sharp interface immersed boundary based incompressible flow solver. Simulations are performed for normal as well as abnormal valves with reduced leaflet motion that models the effect of early leaflet thrombosis. The structure of the aortic jet and the hemodynamic stresses on the aortic wall are analysed to understand the hemodynamic impacts and possible long-term clinical implications of sub-clinical, reduced leaflet motion. The simulation results have shown that the reduced leaflet motion tilts the direction of aortic jet and generates stronger flow separation and re-attachment on the aortic wall downstream from the reduced motion leaflets. The modified flow pattern increases the wall pressure fluctuation and average wall shear stress on the downstream aortic wall, and results in the asymmetric oscillatory shear index distributions, which may have long-term clinical implications such as aortic wall damage and remodelling.