The sensitivity of nonlinear computational models of trabecular bone to tissue level constitutive model

Microarchitectural finite element models have become a key tool in the analysis of trabecular bone. Robust, accurate, and validated constitutive models would enhance confidence in predictive applications of these models and in their usefulness as accurate assays of tissue properties. Human trabecular bone specimens from the femoral neck (n = 3), greater trochanter (n = 6), and lumbar vertebra (n = 1) of eight different donors were scanned by μ-CT and converted to voxel-based finite element models. Unconfined uniaxial compression and shear loading were simulated for each of three different constitutive models: a principal strain-based model, Drucker–Lode, and Drucker–Prager. The latter was applied with both infinitesimal and finite kinematics. Apparent yield strains exhibited minimal dependence on the constitutive model, differing by at most 16.1%, with the kinematic formulation being influential in compression loading. At the tissue level, the quantities and locations of yielded tissue were insensitive to the constitutive model, with the exception of the Drucker–Lode model, suggesting that correlation of microdamage with computational models does not improve the ability to discriminate between constitutive laws. Taken together, it is unlikely that a tissue constitutive model can be fully validated from apparent-level experiments alone, as the calculations are too insensitive to identify differences in the outcomes. Rather, any asymmetric criterion with a valid yield surface will likely be suitable for most trabecular bone models.     

Nonlinear viscoelastic constitutive model for bovine liver tissue

Soft tissue mechanical characterisation is important in many areas of medical research. Examples span from surgery training, device design and testing, sudden injury and disease diagnosis. The liver is of particular interest, as it is the most commonly injured organ in frontal and side motor vehicle crashes, and also assessed for inflammation and fibrosis in chronic liver diseases. Hence, an extensive rheological characterisation of liver tissue would contribute to advancements in these areas, which are dependent upon underlying biomechanical models. The aim of this paper is to define a liver constitutive equation that is able to characterise the nonlinear viscoelastic behaviour of liver tissue under a range of deformations and frequencies. The tissue response to large amplitude oscillatory shear (1–50%) under varying preloads (1–20%) and frequencies (0.5–2 Hz) is modelled using viscoelastic-adapted forms of the Mooney–Rivlin, Ogden and exponential models. These models are fit to the data using classical or modified objective norms. The results show that all three models are suitable for capturing the initial nonlinear regime, with the latter two being capable of capturing, simultaneously, the whole deformation range tested. The work presented here provides a comprehensive analysis across several material models and norms, leading to an identifiable constitutive equation that describes the nonlinear viscoelastic behaviour of the liver.

     

An integrative computational model for intestinal tissue renewal

Objectives:  The luminal surface of the gut is lined with a monolayer of epithelial cells that acts as a nutrient absorptive engine and protective barrier. To maintain its integrity and functionality, the epithelium is renewed every few days. Theoretical models are powerful tools that can be used to test hypotheses concerning the regulation of this renewal process, to investigate how its dysfunction can lead to loss of homeostasis and neoplasia, and to identify potential therapeutic interventions. Here we propose a new multiscale model for crypt dynamics that links phenomena occurring at the subcellular, cellular and tissue levels of organisation.
Methods:  At the subcellular level, deterministic models characterise molecular networks, such as cell-cycle control and Wnt signalling. The output of these models determines the behaviour of each epithelial cell in response to intra-, inter- and extracellular cues. The modular nature of the model enables us to easily modify individual assumptions and analyse their effects on the system as a whole.
Results:  We perform virtual microdissection and labelling-index experiments, evaluate the impact of various model extensions, obtain new insight into clonal expansion in the crypt, and compare our predictions with recent mitochondrial DNA mutation data.
Conclusions:  We demonstrate that relaxing the assumption that stem-cell positions are fixed enables clonal expansion and niche succession to occur. We also predict that the presence of extracellular factors near the base of the crypt alone suffices to explain the observed spatial variation in nuclear beta-catenin levels along the crypt axis.     

A computational framework to investigate retinal haemodynamics and tissue stress

Biomechanics and Modeling in Mechanobiology - The process of vision begins in the retina, yet the role of biomechanical forces in the retina is relatively unknown and only recently being explored....     

A computational method for calculating distensibility of the blood vessel in vivo.

A computational method for calculating the dynamic distensibility of the vessel wall in vivo, developed on the basis of the pressure pulse transmission, is proposed. Distensibilities of descending thoracic aorta, abdominal aorta, and femoral artery in normal dogs, and of femoral artery of a typical dog under the action of vasoactive drugs, have been calculated. In femoral artery it is compared with the values of the diameter change/pressure change. Comparison of the results clearly indicate the feasibility of the proposed method. The order of distensibility found is: descending thoracic aorta greater than abdominal aorta greater than femoral artery.     

A computational framework for cortical learning

Recent physiological findings have revealed that long-term adaptation of the synaptic strengths between cortical pyramidal neurons depends on the temporal order of presynaptic and postsynaptic spikes, which is called spike-timing-dependent plasticity (STDP) or temporally asymmetric Hebbian (TAH) learning. Here I prove by analytical means that a physiologically plausible variant of STDP adapts synaptic strengths such that the presynaptic spikes predict the postsynaptic spikes with minimal error. This prediction error model of STDP implies a mechanism for cortical memory: cortical tissue learns temporal spike patterns if these spike patterns are repeatedly elicited in a set of pyramidal neurons. The trained network finishes these patterns if their beginnings are presented, thereby recalling the memory. Implementations of the proposed algorithms may be useful for applications in voice recognition and computer vision.     

A transversely isotropic hyperelastic constitutive model of the PDL. Analytical and computational aspects

This study describes the development of a constitutive law for the modelling of the periodontal ligament (PDL) and its practical implementation into a commercial finite element code. The constitutive equations encompass the essential mechanical features of this biological soft tissue: non-linear behaviour, large deformations, anisotropy, distinct behaviour in tension and compression and the fibrous characteristics. The approach is based on the theory of continuum fibre-reinforced composites at finite strain where a compressible transversely isotropic hyperelastic strain energy function is defined. This strain energy density function is further split into volumetric and deviatoric contributions separating the bulk and shear responses of the material. Explicit expressions of the stress tensors in the material and spatial configurations are first established followed by original expressions of the elasticity tensors in the material and spatial configurations. As a simple application of the constitutive model, two finite element analyses simulating the mechanical behaviour of the PDL are performed. The results highlight the significance of integrating the fibrous architecture of the PDL as this feature is shown to be responsible for the complex strain distribution observed.     

A computational framework for influenza antigenic cartography

Influenza viruses have been responsible for large losses of lives around the world and continue to present a great public health challenge. Antigenic characterization based on hemagglutination inhibition (HI) assay is one of the routine procedures for influenza vaccine strain selection. However, HI assay is only a crude experiment reflecting the antigenic correlations among testing antigens (viruses) and reference antisera (antibodies). Moreover, antigenic characterization is usually based on more than one HI dataset. The combination of multiple datasets results in an incomplete HI matrix with many unobserved entries. This paper proposes a new computational framework for constructing an influenza antigenic cartography from this incomplete matrix, which we refer to as Matrix Completion-Multidimensional Scaling (MC-MDS). In this approach, we first reconstruct the HI matrices with viruses and antibodies using low-rank matrix completion, and then generate the two-dimensional antigenic cartography using multidimensional scaling. Moreover, for influenza HI tables with herd immunity effect (such as those from Human influenza viruses), we propose a temporal model to reduce the inherent temporal bias of HI tables caused by herd immunity. By applying our method in HI datasets containing H3N2 influenza A viruses isolated from 1968 to 2003, we identified eleven clusters of antigenic variants, representing all major antigenic drift events in these 36 years. Our results showed that both the completed HI matrix and the antigenic cartography obtained via MC-MDS are useful in identifying influenza antigenic variants and thus can be used to facilitate influenza vaccine strain selection. The webserver is available at http://sysbio.cvm.msstate.edu/AntigenMap.     

A computational framework for topographies of cortical areas

Self-organizing feature maps (SOFMs) represent a dimensionality-reduction algorithm that has been used to replicate feature topographies observed experimentally in primary visual cortex (V1). We used the SOFM algorithm to model possible topographies of generic sensory cortical areas containing up to five arbitrary physiological features. This study explored the conditions under which these multi-feature SOFMs contained two features that were mapped monotonically and aligned orthogonally with one another (i.e., “globally orthogonal”), as well as the conditions under which the map of one feature aligned with the longest anatomical dimension of the modeled cortical area (i.e., “dominant”). In a single SOFM with more than two features, we never observed more than one dominant feature, nor did we observe two globally orthogonal features in the same map in which a dominant feature occurred. Whether dominance or global orthogonality occurred depended upon how heavily weighted the features were relative to one another. The most heavily weighted features are likely to correspond to those physical stimulus properties transduced directly by the sensory epithelium of a particular sensory modality. Our results imply, therefore, that in the primary cortical area of sensory modalities with a two-dimensional sensory epithelium, these two features are likely to be organized globally orthogonally to one another, and neither feature is likely to be dominant. In the primary cortical area of sensory modalities with a one-dimensional sensory epithelium, however, this feature is likely to be dominant, and no two features are likely to be organized globally orthogonally to one another. Because the auditory system transduces a single stimulus feature (i.e., frequency) along the entire length of the cochlea, these findings may have particular relevance for topographic maps of primary auditory cortex. This research was supported by The McDonnell Center for Higher Brain Function, The Wallace H. Coulter Foundation and NIH grant DC008880.     

An electromechanical model of cardiac tissue: constitutive issues and electrophysiological effects

We present an electromechanical model of myocardium tissue coupling a modified FitzHugh-Nagumo type system, describing the electrical activity of the excitable media, with finite elasticity, endowed with the capability of describing muscle contractions. The high degree of deformability of the medium makes it mandatory to set the diffusion process in a moving domain, thereby producing a direct influence of the deformation on the electrical activity. Various mechano-electric effects concerning the propagation of cylindrical waves, the rotating spiral waves, and the spiral breakups are discussed.     

Electrospun tecophilic/gelatin nanofibers with potential for small diameter blood vessel tissue engineering

Tissue engineering techniques particularly using electrospun scaffolds have been intensively used in recent years for the development of small diameter vascular grafts. However, the development of a completely successful scaffold that fulfills multiple requirements to guarantee complete vascular regeneration remains challenging. In this study, a hydrophilic and compliant polyurethane namely Tecophilic (TP) blended with gelatin (gel) at a weight ratio of 70:30 (TP(70)/gel(30)) was electrospun to fabricate a tubular composite scaffold with biomechanical properties closely simulating those of native blood vessels. Hydrophilic properties of the composite scaffold induced non‐thrombogenicity while the incorporation of gelatin molecules within the scaffold greatly improved the capacity of the scaffold to serve as an adhesive substrate for vascular smooth muscle cells (SMCs), in comparison to pure TP. Preservation of the contractile phenotype of SMCs seeded on electrospun TP(70)/gel(30) was yet another promising feature of this scaffold. The nanostructured TP(70)/gel(30) demonstrated potential feasibility toward functioning as a vascular graft. © 2014 Wiley Periodicals, Inc. Biopolymers 101: 1165–1180, 2014.     

Urokinase stimulates whereas tissue plasminogen activator attenuates blood vessel stenosis]

Periadventitial application of the urokinase-plasminogen activator (uPA) in pluronic gel to an injured artery stimulated the neointima and neoadventitia formation as well as cell migration and proliferation in vivo. In contrast, the tissue-type plasminogen activator (tPA) reduced the number of neointimal smooth muscle cells and neointimal area and attenuated the lumen stenosis after a balloon catheter injury of the rat carotid artery. This ability to stimulate the neointima and neoadbentitia formation was found to be quite specific for the uPA. The findings suggest that this uPA property provides a specific functional target for attenuating growth of the damage.     

A unifying computational framework for motor control and social interaction

Recent empirical studies have implicated the use of the motor system during action observation, imitation and social interaction. In this paper, we explore the computational parallels between the processes that occur in motor control and in action observation, imitation, social interaction and theory of mind. In particular, we examine the extent to which motor commands acting on the body can be equated with communicative signals acting on other people and suggest that computational solutions for motor control may have been extended to the domain of social interaction.     

A simulated dye method for flow visualization with a computational model for blood flow

A numerical dye method for the visualization of unsteady three-dimensional flow calculations is introduced by coupling the unsteady convection-diffusion equation to the Navier-Stokes equation for mass and momentum. This system of equations is descretized using a finite volume projection-like algorithm with generalized coordinates and overset grids. A powerful pressure prediction method is used to accelerate the convergence of the Pressure Poisson equation. To demonstrate the visualization technique, blood flow through the aortic arch region and the three main arterial branches is computed using various Womersley numbers. In this technique, parcels of fluid are followed in time as a function of the cardiac cycle without having to track individual particles, which in turn aids us to better understand some important aspects of the three-dimensionality of the developing unsteady flow. Using this numerical dye method we analyze the strength of the cross flow during the cardiac cycle, the relationship between the penetration of blood into the aortic branches from its relative position in the ascending aortic region and the effects of the Womersley parameter. This technique can be very useful in the design and development of stents where the topology of the device would require understanding where the blood emanating from the heart ends up at the end of the cardiac cycle. Moreover, this method could be useful in investigating the influence of flow and geometry on the local introduction of medication.     

The embryo makes red blood cell progenitors in every tissue simultaneously with blood vessel morphogenesis

During embryonic life, hematopoiesis occurs first in the yolk sac, followed by the aorto-gonado-mesonephric region, the fetal liver, and the bone marrow. The possibility of hematopoiesis in other embryonic sites has been suspected for a long time. With the use of different methodologies (transgenic mice, electron microscopy, laser capture microdissection, organ culture, and cross-transplant experiments), we show that multiple regions within the embryo are capable of forming blood before and during organogenesis. This widespread phenomenon occurs by hemo-vasculogenesis, the formation of blood vessels accompanied by the simultaneous generation of red blood cells. Erythroblasts develop within aggregates of endothelial cell precursors. When the lumen forms, the erythroblasts "bud" from endothelial cells into the forming vessel. The extensive hematopoietic capacity found in the embryo helps explain why, under pathological circumstances such as severe anemia, extramedullary hematopoiesis can occur in any adult tissue. Understanding the intrinsic ability of tissues to manufacture their own blood cells and vessels has the potential to advance the fields of organogenesis, regeneration, and tissue engineering.