A variational constitutive model for soft biological tissues

In this paper, a fully variational constitutive model of soft biological tissues is formulated in the finite strain regime. The model includes Ogden-type hyperelasticity, finite viscosity, deviatoric and volumetric plasticity, rate and microinertia effects. Variational updates are obtained via time discretization and pre-minimization of a suitable objective function with respect to internal variables. Genetic algorithms are used for model parameter identification due to their suitability for non-convex, high dimensional optimization problems. The material behavior predicted by the model is compared to available tests on swine and human brain tissue. The ability of the model to predict a wide range of experimentally observed behavior, including hysteresis, cyclic softening, rate effects, and plastic deformation is demonstrated.     

A constitutive model for the mechanical behaviour of soft connective tissues

A model of the mechanical behaviour of soft connective tissue has been developed by considering the role of the collagen and glycosaminoglycan (GAG) components within the tissue in order to examine the mechanism by which a variation in the GAG components may exert a control over the mechanical properties of the tissue. It is proposed that the strain energy stored within the collagen fibrils of the loaded tissue can be transferred into a potential field created by the charged GAG components and their electrostatic interaction with the collagen fibrils. A fundamental mechanical unit is described to simulate this energy transfer and a combination of such units is used to represent the tissue. The computer implementation of the proposed tissue model shows it to reproduce many features which have been recognised in the rate dependent mechanical behaviour of soft tissues. These include the characteristic non-linearity of the force-deformation behaviour and the approximate invariance of the stress relaxation behaviour with deformation. The model is also consistent with earlier constitutive representations of tissue behaviour.     

A physically motivated constitutive model for cell-mediated compaction and collagen remodeling in soft tissues

Collagen is the main load-bearing component of many soft tissues and has a large influence on the mechanical behavior of tissues when exposed to mechanical loading. Therefore, it is important to increase our understanding of collagen remodeling in soft tissues to understand the mechanisms behind pathologies and to control the development of the collagen network in engineered tissues. In the present study, a constitutive model was developed by coupling a recently developed model describing the orientation and contractile stresses exerted by cells in response to mechanical stimuli to physically motivated collagen remodeling laws. In addition, cell-mediated contraction of the collagen fibers was included as a mechanism for tissue compaction. The model appeared to be successful in predicting a range of experimental observations, which are (1) the change in transition stretch of periosteum after remodeling at different applied stretches, (2) the compaction and alignment of collagen fibers in tissue-engineered strips, (3) the fiber alignment in cruciform gels with different arm widths, and (4) the alignment of collagen fibers in engineered vascular grafts. Moreover, by changing the boundary conditions, the model was able to predict a helical architecture in the vascular graft without assuming the presence of two helical fiber families a priori. Ultimately, this model may help to increase our understanding of collagen remodeling in physiological and pathological conditions, and it may provide a tool for determining the optimal experimental conditions for obtaining native-like collagen architectures in engineered tissues.     

A discrete-time approach to the formulation of constitutive models for viscoelastic soft tissues

This paper presents a novel approach to constitutive modeling of viscoelastic soft tissues. This formulation combines an anisotropic strain energy function, accounting for preferred material directions, to define the elastic stress–strain relationship, and a discrete time black-box dynamic model, borrowed from the theory of system identification, to describe the time-dependent behavior. This discrete time formulation is straightforwardly oriented to the development of a recursive time integration scheme that calculates the current stress state by using strain and stress values stored at a limited number of previous time instants. The viscoelastic model and the numerical procedure are assessed by implementing two numerical examples, the simulation of a uniaxial tensile test and the inflation of a thin tube. Both simulations are performed using parameter values based on previous experiments on preserved bovine pericardium. Parameters are then adjusted to investigate the sensitivity of the model. The hypotheses the model relies upon are discussed and the main limitations are stated.     

A new constitutive model for multi-layered collagenous tissues

Collagenous tissues such as the aneurysmal wall or the aorta are multi-layered structures with the mean fibre alignments distinguishing one layer from another. A constitutive representation of the multiple collagen layers is not yet developed, and hence the aim of the present study. The proposed model is based on the constitutive theory of finite elasticity and is characterized by an anisotropic strain-energy function which takes the material structure into account. The passive tissue behaviour is modelled and the related mechanical response is assumed to be dominated by elastin and collagen. While elastin is modelled by the neo-Hookean material the constitutive response of collagen is assumed to be transversely isotropic for each individual layer and based on an exponential function. The proposed constitutive function is polyconvex which ensures material stability. The model has five independent material parameters, each of which has a clear physical interpretation: the initial stiffnesses of the collagen fabric in the two principal directions, the shear modulus pertaining to the non-collagenous matrix material, a parameter describing the level of nonlinearity of the collagen fabric, and the angle between the principal directions of the collagen fabric and the reference coordinate system. An extension-inflation test of the adventitia of a human femoral artery is simulated by means of the finite element method and an error function is minimized by adjusting the material parameters yielding a good agreement between the model and the experimental data.     

Finite element implementation of a generalized Fung-elastic constitutive model for planar soft tissues

Numerical simulations of the anisotropic mechanical properties of soft tissues and tissue-derived biomaterials using accurate constitutive models remain an important and challenging research area in biomechanics. While most constitutive modeling efforts have focused on the characterization of experimental data, only limited studies are available on the feasibility of utilizing those models in complex computational applications. An example is the widely utilized exponential constitutive model proposed by Fung. Although present in the biomechanics literature for several decades, implementation of this model into finite element (FE) simulations has been limited. A major reason for limited numerical implementations are problems associated with inherent numerical instability and convergence. To address this issue, we developed and applied two restrictions for a generalized Fung-elastic constitutive model necessary to achieve numerical stability. These are (1) convexity of the strain energy function, and (2) the condition number of material stiffness matrix set lower than a prescribed value. These constraints were implemented in the nonlinear regression used for constitutive model parameter estimation to the experimental biaxial mechanical data. We then implemented the generalized Fung-elastic model into a commercial FE code (ABAQUS, Pawtucket, RI, USA). Single element and multi-element planar biaxial test simulations were conducted to verify the accuracy and robustness of the implementation. Results indicated that numerical convergence and accurate FE implementation were consistently obtained. The present study thus presents an integrated framework for accurate and robust implementation of pseudo-elastic constitutive models for planar soft tissues. Moreover, since our approach is formulated within a general FE code, it can be straightforwardly adopted across multiple software platforms.     

A new constitutive formulation for characterizing the mechanical behavior of soft tissues.

We present a new constitutive formulation that combines certain desirable features of two previously used approaches (phenomenological and microstructural). Specifically, we assume that certain soft tissues can be idealized as composed of various families of noninteracting fibers and a homogeneous matrix. Both the fibers and the matrix are assumed to follow the gross deformation. Within the usual framework of pseudoelasticity, incompressibility, homogeneity, and the continuum hypothesis, a pseudostrain-energy function (W) is proposed wherein W is expressed in terms of matrix and fibrous contributions. Unlike phenomenological approaches where a W is usually chosen in an ad hoc manner, the present approach can be used to postulate reasonable forms of W based on limited structural information and multiaxial stress-strain data. Illustrative applications of the theory are discussed for visceral pleura and myocardium. Concise structurally motivated constitutive relations result, wherein load-dependent anisotropy, nonlinear material behavior, finite deformations, and incompressibility are accounted for.     

A structural viscoelastic model of soft tissues

A non-linear elastic model taking into account the microscopic structure of biological soft tissues is briefly presented and extended to quasi linear viscoelasticity. The modelling of the rheological behavior for near zero stress values is then discussed.     

Inverse analysis of constitutive models: biological soft tissues

The paper describes a procedure for estimating the material parameters of biological soft tissue by fitting model prediction to experimental load-deformation data. This procedure minimizes the error between data and theoretical model prediction through systematically adjusting the parameters in the latter. The procedure uses commercially available software and is not specific to any particular model; nevertheless, for illustration purposes, we employ a six parameter fibril-reinforced poroelastic cartilage model. We are able to estimate any and all of these parameters by the procedure. Convergence of the parameters and convergence of the arbitrary initial stress relaxation to the data was demonstrated in all cases. Though we illustrate the optimization procedure here for unconfined compression only, it can be adapted easily to other experimental configurations such as confined compression, indentation and tensile test. Furthermore, the procedure can be applied in other areas of biomechanics where material parameters need to be extracted from experimental data.     

A cell kinetics model for prostate cancer and its application to clinical data and individual patients

A cell kinetics model is developed to describe the evolution of prostate cancer (PC) from diagnosis to PC specific death. Such a model can be used to estimate an individual's eventual outcome and thus to inform decisions about therapy. To describe the observed clinical progression, the model must postulate three PC cell populations that are (1) local to the prostate and sensitive to hormones, (2) regional and hormone sensitive, and (3) systemic and hormone resistant. A set of coupled first-order differential equations describes the exponential growth of a PC tumor as well as its transformation from a local to systemic disease. The time dependence of the solutions is scaled to the doubling time of the prostate specific antigen (PSADT) because it characterizes the tumor growth for the individual. The conversion from local to systemic cell populations is described with a parameter α that can be associated with the Gleason score. The model also has three critical cell populations that describe (1) the initiation of the non-local populations, (2) the saturation level of the local tumor, and (3) the cell count likely to cause PC specific death. These parameters are calibrated by reproducing published PC clinical data and survival tables. The model is then applied to individuals with complete PC diagnostic data in order to calculate the progression to PC specific death. One man has early stage PC as described in the ‘vignette’ patient of Walsh et al. (2007. N. Engl. J. Med. 357, 2696-2705). The second man has a more serious condition and has undergone both local and systemic treatments. Unfortunately, I am that patient.     

A recruitment-based rheological model for mechanical behavior of soft tissues

When lung tissue is subjected to finite deformations, phenomena appear that can only be described using nonlinear models. This paper considers the lung as a material composed of two elements, a continuous phase that acts uninterruptedly and a second phase composed of fiber elements that are recruited progressively into the mechanical process. Each individual fiber participates in the mechanical response of the set only when the deformation is above a certain value. A nine-parameter model was designed adopting standard viscoelastic elements both for the matrix and for each of the fibers. The mechanical behavior of the lung can be reproduced by a fitting process with standard numerical procedures in both dynamic-mechanical measurements and stress relaxation processes. Mechanical stress relaxation tests and dynamic-mechanical measurements have been carried out on subpleural parenchymal strips from rat lung. The model permits the reproduction of lung behavior in both types of measurements. The results show a recruitment ratio that decreases with deformation and the nonparticipation of the parallel matrix fraction in the lung's mechanical response so that a uniaxial transmission of force in the lung occurs via the recruited elements and the matrix series.     

Simulation of planar soft tissues using a structural constitutive model: Finite element implementation and validation

Computational implementation of physical and physiologically realistic constitutive models is critical for numerical simulation of soft biological tissues in a variety of biomedical applications. It is well established that the highly nonlinear and anisotropic mechanical behaviors of soft tissues are an emergent behavior of the underlying tissue microstructure. In the present study, we have implemented a structural constitutive model into a finite element framework specialized for membrane tissues. We noted that starting with a single element subjected to uniaxial tension, the non-fibrous tissue matrix must be present to prevent unrealistic tissue deformations. Flexural simulations were used to set the non-fibrous matrix modulus because fibers have little effects on tissue deformation under three-point bending. Multiple deformation modes were simulated, including strip biaxial, planar biaxial with two attachment methods, and membrane inflation. Detailed comparisons with experimental data were undertaken to insure faithful simulations of both the macro-level stress–strain insights into adaptations of the fiber architecture under stress, such as fiber reorientation and fiber recruitment. Results indicated a high degree of fidelity and demonstrated interesting microstructural adaptions to stress and the important role of the underlying tissue matrix. Moreover, we apparently resolve a discrepancy in our 1997 study (Billiar and Sacks, 1997. J. Biomech. 30 (7), 753–756) where we observed that under strip biaxial stretch the simulated fiber splay responses were not in good agreement with the experimental results, suggesting non-affine deformations may have occurred. However, by correctly accounting for the isotropic phase of the measured fiber splay, good agreement was obtained. While not the final word, these simulations suggest that affine fiber kinematics for planar collagenous tissues is a reasonable assumption at the macro level. Simulation tools such as these are imperative in the design and simulation of native and engineered tissues.     

A Cox regression model for the relative mortality and its application to diabetes mellitus survival data

A Cox-type regression model for the ratio between the mortality in a cohort and that in a reference population is introduced. By means of the model it is possible to include in the survival analysis both individual (possibly time-dependent) characteristics for the study cohort and changing trends in the mortality in the reference population. This is particularly relevant in long-term follow-up studies where there may be considerable changes in the mortality in the reference population. Estimation procedures in the model are discussed and large-sample properties of the estimators are outlined. The model is applied to the analysis of two sets of data concerning the survival among insulin-dependent diabetics in Denmark.     

A tethered adhesive particle model of two-dimensional elasticity and its application to the erythrocyte membrane.

A new model of two-dimensional elasticity with application to the erythrocyte membrane is proposed. The system consists of a planar array of self-adhesive particles attached to nearest neighbors with flexible tethers. Stretching from the equilibrium dimension is resisted because force is required to dissociate the particle clusters and to decrease the distribution entropy. Release of the external force is accompanied by a contraction as thermal diffusion randomizes the particles and allows interparticle attachments to form again. Analysis of membrane thermodynamics and mechanics under the two-state particle assumption results in a shear softening stress-strain relation. The shear modulus is found proportional to the square root of the surface density of particles, the interparticle adhesive energy, and is inversely proportional to the tether length. Applied to the erythrocyte membrane under the assumption that band 3 tetramer represents the particle and spectrin the tether, the shear modulus predicted corresponds to the measured value when the interparticle adhesive energy is approximately 4.0-5.9 kT, where kT is the Boltzmann constant multiplied by the temperature. This model suggests a mechanism wherein erythrocyte membrane deformability depends on integral protein homomultimeric interactions and can be modulated from the external surface.     

A cell-based constitutive relation for bio-artificial tissues

By using a combination of continuum and statistical mechanics we derive an integral constitutive relation for bio-artificial tissue models consisting of a monodisperse population of cells in a uniform collagenous matrix. This constitutive relation quantitatively models the dependence of tissue stress on deformation history, and makes explicit the separate contribution of cells and matrix to the mechanical behavior of the composite tissue. Thus microscopic cell mechanical properties can be deduced via this theory from measurements of macroscopic tissue properties. A central feature of the constitutive relation is the appearance of "anisotropy tensors" that embody the effects of cell orientation on tissue mechanics. The theory assumes that the tissues are stable over the observation time, and does not in its present form allow for cell migration, reorientation, or internal remodeling. We have compared the predictions of the theory to uniaxial relaxation tests on fibroblast-populated collagen matrices (FPMs) and find that the experimental results generally support the theory and yield values of fibroblast contractile force and stiffness roughly an order of magnitude smaller than, and viscosity comparable to, the corresponding properties of active skeletal muscle. The method used here to derive the tissue constitutive equation permits more sophisticated cell models to be used in developing more accurate representations of tissue properties.     

A structural constitutive model for collagenous cardiovascular tissues incorporating the angular fiber distribution

Accurate constitutive models are required to gain further insight into the mechanical behavior of cardiovascular tissues. In this study, a structural constitutive framework for cardiovascular tissues is introduced that accounts for the angular distribution of collagen fibers. To demonstrate its capabilities, the model is applied to study the biaxial behavior of the arterial wall and the aortic valve. The pressure-radius relationships of the arterial wall accurately describe experimentally observed sigma-shaped curves. In addition, the nonlinear and anisotropic mechanical properties of the aortic valve can be analyzed with the proposed model. We expect that the current model offers strong possibilities to further investigate the complex mechanical behavior of cardiovascular tissues, including their response to mechanical stimuli.     

A model of fracture testing of soft viscoelastic tissues

Fracture, or tear, toughness of soft tissues can be computed from the work of fracture divided by the area of new crack surface. For soft tissues without significant plastic deformation, total work, which can be measured experimentally, is composed of the sum of fracture and viscoelastic work. In order to deduce fracture work, a method is needed to estimate viscoelastic work.Two different methods (Ph.D. Dissertation, University of Minnesota, 2000; J. Mater. Sci.: Mater. Med. 12 (2001) 327) have been proposed to estimate viscoelastic work in a fracture test of a soft tissue. The relative merits of these methods are unknown because the true viscoelastic work in an experiment is unknown. In order to characterize the accuracy of these methods, a theoretical model of crack propagation of viscoelastic soft tissue in a tensile test is presented, from which the exact viscoelastic work is calculated. The material is assumed to obey the standard linear solid model.The "exact" solution for the viscoelastic work during the fracture is computed from the model and compared with the work estimated by the two methods. It was found that both methods tend to underestimate the viscoelastic work done, and thus overestimate the fracture work and fracture toughness, although the errors were greater with the Fedewa method. It was further found that low displacement rates can give rise to a "snap" effect, where rapid crack growth can cause a disproportionate amount of viscoelastic energy to be dissipated during unloading. This modeling approach may be useful in evaluating other experimental methods of soft tissue fracture.     

Dissimilarity for partially ranked data and its application to cover-abundance data

Cover-abundance estimates are commonly employed in phytosociological investigations to record the performance of species. Because the coded values are on an ordinal scale of measure, various authors have suggested that some transformation is necessary before such values can be used for classification and ordination. However, it is not clear that transformation is a sufficient treatment, and it would seem preferable to use ordinal data directly. In this paper we examine such direct use of partial rankings and show that several dissimilarity measures can be defined for this case without invoking any transformations. They include dissimilarity measures associated with various rank correlation measures and with distances between strings; all the measure are variant forms of Hausdorf's interset distance. Certain other kinds of data, such as those employing dominant and subdominant species and the dry-weight-rank estimation of biomass, are also on an ordinal scale and could be analysed using similar techniques.To illustrate the approach, a string dissimilarity measure is used to analyse a set of data from Slovakian grasslands which appear to reflect a simple gradient. The original data were recorded with 10 classes of performance and are analysed using hierarchical and nondeterministic, overlapping, classifications.     

A theoretical model for the elastic properties of very soft tissues.

A theoretical model is developed to predict the elastic properties of very soft tissues such as glands, tumors and brain. Tissues are represented as regular arrays of polyhedral (cubic or tetrakaidecahedral) cells, surrounded by extracellular spaces of uniform width. Cells are assumed to be incompressible, with very low resistance to shear deformation. Tissue shear rigidity is assumed to result mainly from the extracellular matrix, which is treated as a compressible elastic mesh of interconnected fibers. Small-strain elastic properties of tissue are predicted using a finite-element method and an analytical method. The model can be used to estimate the compressibility of a very soft tissue based on its Young's modulus and extracellular volume fraction.