Modeling of growth and remodeling in soft biological tissues with multiple constituents

Among the various important characteristics of biological tissues is their ability to grow and remodel. It is well-known that one of the primary triggers behind the growth and remodeling process is changes in the mechanical environment, for instance changes in stress, strain, etc. These mechanisms of mechanotransduction are the driving force behind many changes in structure and function including growth and remodeling. The purpose of this article is to formulate better constitutive equations for the stress in tissues with multiple constituents undergoing growth and remodeling. This is a very complex problem and is of tremendous importance. Here, we do the modeling from a mechanics point of view, utilizing the theory of natural configurations coupled with population dynamics to accurately model the production and removal of the different constituents that comprise the tissue. This is accomplished by deriving a generalized McKendrick equation for growth and remodeling and has the advantage of directly including the age distribution of constituents into the model. The population distribution function is then used to determine the stress in the tissue.     

Constitutive branching in compressible elastic materials

Summary Branching analysis for the homogeneous deformations of a compressible elastic unit cube under dead loading is performed. Critical conditions for branching of the equilibrium paths are derived and the post-critical equilibrium paths are described. Special attention is given to the compound branching.     

Symmetry limit theory for cantilever beam-columns subjected to cyclic reversed bending

The behavior of a linear strain-hardening cantilever beam-column subjected to completely reversed plastic bending of a new idealized program under constant axial compression consists of three stages: a sequence of symmetric steady states, a subsequent sequence of asymmetric steady states and a divergent behavior involving unbounded growth of an anti-symmetric deflection mode. A new concept “symmetry limit” is introduced here as the smallest critical value of the tip-deflection amplitude at which transition from a symmetric steady state to an asymmetric steady state can occur in the response of a beam-column. A new theory is presented for predicting the symmetry limits. Although this transition phenomenon is phenomenologically and conceptually different from the branching phenomenon on an equilibrium path, it is shown that a symmetry limit may theoretically be regarded as a branching point on a “steady-state path” defined anew. The symmetry limit theory and the fundamental hypotheses are verified through numerical analysis of hysteretic responses of discretized beam-column models.     

Engineering models for synthetic microvascular materials with interphase mass,momentum and energy transfer

New materials are being developed that consist of a solid matrix with pores or vessels through which a functional fluid phase may pass. The fluid can provide expanded functionality such as healing and remodeling, damage disclosure, enhanced heat transfer, and controlled deformation, stiffness and damping. This paper presents a class of engineering models for synthetic microvascular materials that have fluid passages much smaller than a characteristic structural length such as panel thickness. The materials are idealized as two-phase continua with a solid phase and a fluid phase occupying every volume. The model permits the solid and fluid phases to exchange mass, momentum and energy. Balance equations and the entropy inequality for general mixtures are taken from existing continuum mixture theory. These are augmented with certain definite types of solid–fluid interactions in order to enable adequately general, but workable, engineering analysis. The thermomechanical characteristics of this restricted class of materials are delineated. By demanding that the law of increase of entropy be satisfied for all processes, much is deduced about the acceptable forms of constitutive equations and internal state variable evolution equations. The paper concludes with a study of the uniaxial tension behavior of an idealized vascular material.     

Bone remodeling I: theory of adaptive elasticity

A thermomechanical continuum theory involving a chemical reaction and mass transfer between two constituents is developed here as a model for bone remodeling. Bone remodeling is a collective term for the continual processes of growth, reinforcement and resorbtion which occur in living bone. The resulting theory describes an elastic material which adapts its structure to applied loading.

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Zusammenfassung Eine Thermo-mechanische kontinuum Theorie als Modell für die Knochenrekonstrucktion wird entwickelt, die eine chemische Reaktion und einen Massentransport zwischen zwei Komponenten behandelt. Knochenrekonstruktion ist ein Sammelbegriff für die kontinuierlichen Prozesse des Wachsens, der Verstärkung und des Abbaus wie sie im lebenden Knochen auftreten. Die Theorie beschreibt ein elastisches Material, das sich in der Form der Belastung anpasst.

     

A theoretical model for surface bone remodeling under electromagnetic loads

A theoretical model for surface bone remodeling under electromagnetic loads is proposed in this paper. In the model, surface bone remodeling is assumed to be related to growth factors. Growth factors in latent form in osteocytes are released to the bone fluid after the osteocytes are absorbed by osteoclasts, and then regulate the bone formation process. At the same time, environmental loadings can influence the generation of growth factors. This paper shows how surface bone remodeling is triggered under the influence of growth factors. Based on this hypothesis, a computational model is established that simulates the bone coupling remodeling process, including internal and surface bone remodeling. The effects of various loadings, including electrical and magnetic loadings, are simulated and compared. The interactions between internal and surface bone remodeling are investigated via the numerical method. The results indicate that an electromagnetic field can strongly influence the bone remodeling process and that the remodeling process will be altered after surface bone remodeling is triggered, compared to the sole effect of the internal remodeling process.     

On the singularities of a constrained (incompressible-like) tensegrity-cytoskeleton model under equitriaxial loading

Singularity theory is applied for the study of the characteristic three-dimensional tensegrity-cytoskeleton model after adopting an incompressibility constraint. The model comprises six elastic bars interconnected with 24 elastic string members. Previous studies have already been performed on non-constrained systems; however, the present one allows for general non-symmetric equilibrium configurations. Critical conditions for branching of the equilibrium are derived and post-critical behaviour is discussed. Classification of the simple and compound singularities of the total potential energy function is effected. The theory is implemented into the cusp catastrophe for the case of one-dimensional branching of the buckling-allowed tensegrity model, and an elliptic umbilic singularity for compound branching of a rigid-bar model. It is pointed out that singularity studies with constraints demand a quite different mathematical approach than those without constraints.     

热载荷作用下梯度多孔材料梁弯曲及过屈曲力学行为的研究

基于Bernoulli-Euler梁理论,引入物理中面解耦了复合材料结构的面内变形与横向弯曲特性,研究了梯度多孔材料矩形截面梁在热载荷作用下的弯曲及过屈曲力学行为．假设沿梁厚度方向材料的性质是连续变化的,利用能量法推导了矩形截面梁的控制微分方程和边界条件,并用打靶法对无量纲化的控制方程进行数值求解．利用计算得到的结果分析了材料的性质、热载荷、边界条件对矩形截面梁非线性力学行为的影响．结果表明,对称材料模型下,固支梁与简支梁均显示出了典型的分支屈曲行为特征,而其临界屈曲热载荷值均会随着孔隙率系数的增加而单调增加．非对称材料模型下,固支梁仍显示出分支屈曲行为特征,但其临界屈曲热载荷不再随着孔隙率系数的变化而单调变化;而对于两端简支梁,发生了弯曲变形,弯曲挠度随载荷的增大而增大．     

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.     

Brittle fracture dynamics with arbitrary paths. II. Dynamic crack branching under general antiplane loading

The dynamic propagation of a bifurcated crack under antiplane loading is considered. The dependence of the stress intensity factor just after branching is given as a function of the stress intensity factor just before branching, the branching angle and the instantaneous velocity of the crack tip. The jump in the dynamic energy release rate due to the branching process is also computed. Similar to the single crack case, a growth criterion for a branched crack is applied. It is based on the equality between the energy flux into each propagating tip and the surface energy which is added as a result of this propagation. It is shown that the minimum speed of the initial single crack which allows branching is equal to 0.39c, where c is the shear wave speed. At the branching threshold, the corresponding bifurcated cracks start their propagation at a vanishing speed with a branching angle of approximately 40°.     

Bifurcational instability of an atomic lattice

In a recent article N.H. Macmillan and A. Kelly (1972) have confirmed on the basis of a linear eigenvalue analysis that a mechanically stressed perfect crystal can exhibit a bifurcational instability at stresses ranging to 20 per cent below that of the limiting maximum of the primary stress-strain curve. The question thus arises as to whether the branching point is in a non-linear sense either stable or unstable. In the former case, perfect and slightly imperfect crystals would be capable of sustaining stresses over and above the eigenvalue critical stress. In the unstable case, however, this eigenvalue stress would represent the ultimate strength of a perfect solid, while an imperfect crystal would fail at a limiting stress substantially below the eigenvalue.At 20 per cent below the limit point such a branching point is essentially distinct, and the non-linear stability analysis needed to answer this question is provided by a recently established general branching theory for discrete conservative systems. Often, however, the two critical equilibrium states are much nearer than this, and the branching theory is here suitably extended to cover the case of near-compound instabilities.An illustrative study of a close-packed crystal under uniaxial tension is next presented. A kinematically-admissible displacement field is employed and a bifurcation point is located on the primary equilibrium path just before the limiting maximum, the eigenvector being associated with a transverse shearing strain. Under these conditions a corresponding small transverse shearing stress would represent an ‘imperfection’, and the non-linear branching problem is next studied using the new general theory. This shows (in excellent quantitative agreement with an ad hoc numerical solution) that the branching point is non-linearly unstable with a quite severe imperfection-sensitivity which manifests itself as a sharp cusp on the failure-stress locus.     

Effect of magnetic field on poroelastic bone model for internal remodeling

This paper studies the effects of the magnetic field and the porosity on a poroelastic bone model for internal remodeling. The solution of the internal bone remodeling process induced by a magnetic field is presented. The bone is treated as a poroelastic material by Biot’s formulation. Based on the theory of small strain adaptive elasticity, a theoretical approach for the internal remodeling is proposed. The components of the stresses, the displacements, and the rate of internal remodeling are obtained in analytical forms, and the numerical results are represented graphically. The results indicate that the effects of the magnetic field and the porosity on the rate of internal remodeling in bone are very pronounced.     

Residual stresses in soft tissue as a consequence of growth and remodeling: application to an arterial geometry

We develop a thermodynamically consistent model for growth and remodeling in elastic arteries. The model is specialized to a cylindrical geometry, strain energy of the Holzapfel–Gasser–Ogden type and remodeling of the collagen fiber angle. A numerical method for calculating the evolution of the adaptation process is developed. For a particular choice of the thermodynamic forces of growth and remodeling (configurational forces), it is shown that an almost homogeneous transmural axial and tangential stress distribution is obtained. Residual stresses develop during this adaption process and these resemble what is found in experiments and by parameter identification methods.     

Growth,mass transfer,and remodeling in fiber-reinforced,multi-constituent materials

We represent a biological tissue by a multi-constituent, fiber-reinforced material, in which we consider two phases: fluid, and a fiber-reinforced solid. Among the various processes that may occur in such a system, we study growth, mass transfer, and remodeling. To us, mass transfer is the reciprocal exchange of constituents between the phases, growth is the variation of mass of the system in response to interactions with the surrounding environment, and remodeling is the evolution of its internal structure. We embrace the theory according to which these events, which lead to a structural reorganization of the system and anelastic deformations, require the introduction of balance laws, which complete the physical picture offered by the standard ones. The former are said to be non-standard. Our purposes are to determine the rates of anelastic deformation related to mass transfer and growth, and to study fiber reorientation in the case of a statistical distribution of fibers. In particular, we discuss the use of the non-standard balance laws in modeling transfer of mass, and compare our results with a formulation in which such balance laws are not introduced.     

Elements of a finite strain-gradient thermomechanical theory for material growth and remodeling

A second-gradient theory in finite strains is proposed to deal with the phenomena of material growth and remodeling, as happens in biomechanics, on account of mass transport and morphogenetic species. It involves first-order and second-order transplants (local structural rearrangements) and two material connections on the material manifold. It is shown that the evolution of these structural changes or “material inhomogeneities” is governed by Eshelby-like stress and hyperstress tensors. A thermodynamically admissible set of constitutive equations is proposed. The complexity due to the finite-strain gradient theory is a necessity in order to accommodate mass exchanges and diffusion of species.     

A percolation-type fracture criterion for composites with randomly oriented fibres

A fracture model is built up for a solid composed of brittle fibres randomly oriented in the matrix volume. The fracture process includes a stable growth of microcracks caused by fibre breaking under the load and formation of an infinite cluster of the microcracks. Both upper and lower bounds for ultimate stress in a fibre system are found as functions of the fibre volume fraction. The calculation of the ultimate stresses are performed by using the percolation theory and the theory of branching processes. At the present stage of the theory under consideration, only two types of the microcracks are appraised, namely that of a delamination type which corresponds to a weak fibre/matrix interface, and that of a penny shape which corresponds to a strong fibre/matrix interface. A particular solid contains only one type of the microcracks. In both cases, non-linear dependencies of the ultimate composite strength on fibre volume fraction are obtained.     

Perspectives on biological growth and remodeling

The continuum mechanical treatment of biological growth and remodeling has attracted considerable attention over the past fifteen years. Many aspects of these problems are now well-understood, yet there remain areas in need of significant development from the standpoint of experiments, theory, and computation. In this perspective paper we review the state of the field and highlight open questions, challenges, and avenues for further development.     

基于应变能准则优化模型的骨骼重建数值模拟

将骨骼重建的适应性弹性理论及参考应变能理论与结构优化及有限元方法结合,建立了基于应变能准则优化模型的骨骼重建数值模拟方法,研究骨骼内部重建的机理和规律。以单元应变能密度为刺激源,由内部材料的分布变化来模拟骨重建的过程和规律。通过对股骨头重建的数值模拟,取得了与临床实验相符的结果,也证实了骨结构形态是对力学环境的最佳适应,定量地反映了力学刺激对骨骼重建的影响,得到了符合骨骼重建规律的结论。     

Mass transport in morphogenetic processes: A second gradient theory for volumetric growth and material remodeling

In this work, we derive a novel thermo-mechanical theory for growth and remodeling of biological materials in morphogenetic processes. This second gradient hyperelastic theory is the first attempt to describe both volumetric growth and mass transport phenomena in a single-phase continuum model, where both stress- and shape-dependent growth regulations can be investigated. The diffusion of biochemical species (e.g. morphogens, growth factors, migration signals) inside the material is driven by configurational forces, enforced in the balance equations and in the set of constitutive relations. Mass transport is found to depend both on first- and on second-order material connections, possibly withstanding a chemotactic behavior with respect to diffusing molecules. We find that the driving forces of mass diffusion can be written in terms of covariant material derivatives reflecting, in a purely geometrical manner, the presence of a (first-order) torsion and a (second-order) curvature. Thermodynamical arguments show that the Eshelby stress and hyperstress tensors drive the rearrangement of the first- and second-order material inhomogeneities, respectively. In particular, an evolution law is proposed for the first-order transplant, extending a well-known result for inelastic materials. Moreover, we define the first stress-driven evolution law of the second-order transplant in function of the completely material Eshelby hyperstress.The theory is applied to two biomechanical examples, showing how an Eshelbian coupling can coordinate volumetric growth, mass transport and internal stress state, both in physiological and pathological conditions. Finally, possible applications of the proposed model are discussed for studying the unknown regulation mechanisms in morphogenetic processes, as well as for optimizing scaffold architecture in regenerative medicine and tissue engineering.