О величине зазора в распределительном узле аксиально-поршневых гидромашин

Тез. докл. Междунар. науч.-техн. конф. (науч. чтения, посвящ. П. О. Сухому), Гомель, 4-6 июля. 2002 г

Computational investigations of variability in mechanobiological simulations of tissue differentiation

THESIS 9633Theories of mechanoregulation have been integrated in computational models of mechanobiological experiments to test hypotheses of mechanobiology. It is believed that computational models need to be improved by considering the variability reported in animal experiments in order to enhance corroboration of hypotheses and to enable the use of computational models in practical bioengineering applications

Primary cilia mechanics affects cell mechanosensation: A computational study.

Primary cilia (PC) are mechanical cell structures linked to the cytoskeleton and are central to how cells sense biomechanical signals from their environment. However, it is unclear exactly how PC mechanics influences cell mechanosensation. In this study we investigate how the PC mechanical characteristics are involved in the mechanotransduction process whereby cilium deflection under fluid flow induces strains on the internal cell components that regulate the cell׳s mechanosensitive response. Our investigation employs a computational approach in which a finite element model of a cell consisting of a nucleus, cytoplasm, cortex, microtubules, actin bundles and a primary cilium was used together with a finite element representation of a flow chamber. Fluid-structure interaction analysis was performed by simulating perfusion flow of 1mm/s on the cell model. Simulations of cells with different PC mechanical characteristics, showed that the length and the stiffness of PC are responsible for the transmission of mechanical stimuli to the cytoskeleton. Fluid flow deflects the cilium, with the highest strains found at the base of the PC and in the cytoplasm. The PC deflection created further strains on the cell nucleus but did not influence microtubules and actin bundles significantly. Our results indicate that PC deflection under fluid flow stimulation transmits mechanical strain primarily to other essential organelles in the cytoplasm, such as the Golgi complex, that regulate cells' mechanoresponse. The simulations further suggest that cell mechanosensitivity can be altered by targeting PC length and rigidity

Predicting the effect of reduced load level and cell infiltration on spatio-temporal Achilles tendon healing

Mechanobiology plays an important role in tendon healing. However, the relationship between mechanical loading and spatial and temporal evolution of tendon properties during healing is not well understood. This study builds on a recently presented mechanoregulatory computational framework that couples mechanobiological tendon healing to tissue production and collagen orientation. In this study, we investigated how different magnitudes of mechanical stimulation (principal strain) affect the spatio-temporal evolution of tissue production and the temporal evolution of elastic and viscoelastic mechanical parameters. Specifically, we examined the effect of cell infiltration (mimicking migration and proliferation) in the callus on the resulting tissue production by modeling production to depend on local cell density. The model predictions were carefully compared with experimental data from Achilles tendons in rats, at 1, 2 and 4 weeks of healing. In the experiments, the rat tendons had been subjected to free cage activity or reduced load levels through intramuscular botox injections. The simulations that included cell infiltration and strain-regulated collagen production predicted spatio-temporal tissue distributions and mechanical properties similarly to that observed experimentally. In addition, lack of matrix-producing cells in the tendon core during early healing may result in reduced collagen content, regardless of the daily load level. This framework is the first to computationally investigate mechanobiological mechanisms underlying spatial and temporal variations during tendon healing for various magnitudes of loading. This framework will allow further characterization of biomechanical, biological, or mechanobiological processes underlying tendon healing

Understanding how reduced loading affects Achilles tendon mechanical properties using a fibre-reinforced poro-visco-hyper-elastic model

Understanding tendon mechanobiology is important for gaining insight into the development of tendon pathology and subsequent repair processes. The aim of this study was to investigate how experimentally observed mechanobiological adaptation of rat Achilles tendons translate to changes in constitutive mechanical properties and biomechanical behavior. In addition, we assessed the ability of the model to simulate tendon creep and stress-relaxation. A three dimensional finite element framework of rat Achilles tendon was implemented with a fibre-reinforced poro-visco-hyper-elastic constitutive model. Stress-relaxation and creep data from Achilles tendons of Sprague Dawley rats that had been subjected to both daily loading and a period of reduced loading were used to determine the constitutive properties of the tendons. Our results showed that the constitutive model captures creep and stress-relaxation data from rat Achilles tendons for both loaded and unloaded tendons with good accuracy (normalized root mean square error between model and experimental data were 0.010–0.027). Only when the model parameters were fitted to data from both mechanical tests simultaneously, were we able to also capture similar increase in elastic energy (increased stiffness)and decreased viscoelasticity in response to unloading, as was reported experimentally. Our study is the first to show that experimentally observed mechanobiological changes in tendon biomechanics, such as stiffness and viscoelasticity, can be designated to mechanical quantities in a constitutive model. Further investigation in this direction has potential to discriminate tissue components responsible for specific biomechanical response, and enable targeted treatment strategies for tendon health

Corroboration of computational models for mechanoregulated stem cell differentiation

Do computational models contribute to progress in mechanobiology? Jacobs and Kelly (in Advances on Modelling in Tissue Engineering, p. 1–14, 2011) suggest that they do, but at the same time propose a limitation in the form of the ‘paradox of validation’, whereby the information needed to validate mechanoregulation theories obviates the need for them in the first place. In this article, the corroboration of theories describing mechanoregulation of tissue differentiation is reviewed. Considering the falsifiability of computational models derived using the theories as a measure of their predictive power, it is shown that the predictive power of some theories is poor and that models based on these theories fall into the ‘paradox of validation’. Week theories for any phenomenon would succumb to such a paradox. We argue that mechanobiology needs theories that can have more potentially falsifying experiments and that perhaps the discipline does suffer from theories that are a priori designed to minimise falsifiability. However, several theories do have predictive power beyond the data used to validate them, so a paradox of validation should disappear as the subject develops

Substrate stiffness and oxygen availability as regulators of mesenchymal stem cell differentiation within a mechanically loaded bone chamber

Mechanical stimuli such as tissue deformation and fluid flow are often implicated as regulators of mesenchymal stem cell (MSC) differentiation during regenerative events in vivo. However, in vitro studies have identified several other physical and biochemical environmental cues, such as substrate stiffness and oxygen availability, as key regulators of stem cell fate. Hypotheses for how MSC differentiation is regulated in vivo can be either corroborated or rejected based on the ability of in silico models to accurately predict spatial and temporal patterns of tissue differentiation observed experimentally. The goal of this study was to employ a previously developed computational framework to test the hypothesis that substrate stiffness and oxygen availability regulate stem cell differentiation during tissue regeneration within an implanted bone chamber. To enable a prediction of the oxygen levels within the bone chamber, a lattice model of angiogenesis was implemented where blood vessel progression was dependent on the local mechanical environment. The model successfully predicted key aspects of MSC differentiation, including the correct spatial development of bone, marrow and fibrous tissue within the unloaded bone chamber. The model also successfully predicted chondrogenesis within the chamber upon the application of mechanical loading. This study provides further support for the hypothesis that substrate stiffness and oxygen availability regulate stem cell differentiation in vivo. These simulations also highlight the indirect role that mechanics may play in regulating MSC fate by inhibiting blood vessel progression and hence disrupting oxygen availability within regenerating tissues

Comparison of structural anisotropic soft tissue models for simulating Achilles tendon tensile behaviour

The incidence of tendon injury (tendinopathy) has increased over the past decades due to greater participation in sports and recreational activities. But little is known about the aetiology of tendon injuries because of our limited knowledge in the complex structure-function relationship in tendons. Computer models can capture the biomechanical behaviour of tendons and its structural components, which is essential for understanding the underlying mechanisms of tendon injuries. This study compares three structural constitutive material models for the Achilles tendon and discusses their application on different biomechanical simulations. The models have been previously used to describe cardiovascular tissue and articular cartilage, and one model is novel to this study. All three constitutive models captured the tensile behaviour of rat Achilles tendon (root mean square errors between models and experimental data are 0.50-0.64). They further showed that collagen fibres are the main load-bearing component and that the non-collagenous matrix plays a minor role in tension. By introducing anisotropic behaviour also in the non-fibrillar matrix, the new biphasic structural model was also able to capture fluid exudation during tension and high values of Poisson's ratio that is reported in tendon experiments

Corroboration of mechanobiological simulations of tissue differentiation in an in vivo bone chamber using a lattice-modeling approach

It is well established that the mechanical environment modulates tissue differentiation, and a number of mechanoregulatory theories for describing the process have been proposed. In this study, simulations of an in vivo bone chamber experiment were performed that allowed direct comparison with experimental data. A mechanoregulation theory for mesenchymal stem cell differentiation based on a combination of fluid flow and shear strain (computed using finite element analysis) was implemented to predict tissue differentiation inside mechanically controlled bone chambers inserted into rat tibae. To simulate cell activity, a lattice approach with stochastic cell migration, proliferation, and selected differentiation was adopted; because of its stochastic nature, each run of the simulation gave a somewhat different result. Simulations predicted the load-dependency of the tissue differentiation inside the chamber and a qualitative agreement with histological data; however, the full variability found between specimens in the experiment could not be predicted by the mechanoregulation algorithm. This result raises the question whether tissue differentiation predictions can be linked to genetic variability in animal populations

Crack propagation in cortical bone is affected by the characteristics of the cement line : a parameter study using an XFEM interface damage model

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