Mesenchymal stem cells (MSCs) within their native environment of the stem cell niche in bone receive biochemical stimuli from surrounding cells. These stimuli likely influence how MSCs differentiate ...to become bone precursors. The ability of MSCs to undergo osteogenic differentiation is well established in vitro;however, the role of the natural cues from bone's regulatory cells, osteocytes and osteoblasts in regulating the osteogenic differentiation of MSCs in vivo are unclear. In this study we delineate the role of biochemical signalling from osteocytes and osteoblasts, using conditioned media and co-culture experiments, to understand how they direct osteogenic differentiation of MSCs. Furthermore, the synergistic relationship between osteocytes and osteoblasts is examined by transwell co-culturing of MSCs with both simultaneously. Osteogenic differentiation of MSCs was quantified by monitoring alkaline phosphatase (ALP) activity, calcium deposition and cell number. Intracellular ALP was found to peak earlier and there was greater calcium deposition when MSCs were co-cultured with osteocytes rather than osteoblasts, suggesting that osteocytes are more influential than osteoblasts in stimulating osteogenesis in MSCs. Osteoblasts initially stimulated an increase in the number of MSCs, but ultimately regulated MSC differentiation down the same pathway. Our novel co-culture system confirmed a synergistic relationship between osteocytes and osteoblasts in producing biochemical signals to stimulate the osteogenic differentiation of MSCs. This study provides important insights into the mechanisms at work within the native stem cell niche to stimulate osteogenic differentiation and outlines a possible role for the use of co-culture or conditioned media methodologies for tissue engineering applications.
Fatigue crack nucleation in polycrystal ferritic steel is investigated through experimental observation of multiple large-grained, notched, four-point bend tests combined with explicit ...microstructural representation of the same samples using crystal plasticity finite element techniques in order to assess fatigue indicator parameters, together with the roles of elastic anisotropy and length scale effects in slip development, and hence in crack nucleation.
Elastic anisotropy has been demonstrated to play a pivotal role in the distribution and magnitude of polycrystal slip relative to observed crack nucleation sites in the context of constrained cyclic microplasticity. Length scale effects were found not to alter substantively the distributions or magnitudes of slip relative to the observed crack nucleation site, but in detailed analyses of an experimental sample, the location of highest magnitude of geometrically necessary dislocations was found to coincide precisely with the position of predicted peak plasticity and the experimentally observed crack nucleation site.
The distributions of microplasticity within polycrystal samples were found to change quite significantly between the first yield and after multiple cycles. As a result, the effective plastic strain per cycle was found to be a better indicator of fatigue crack nucleation than peak effective plastic strain. In nine independently tested and analysed polycrystal samples, the cyclic effective plastic strain and crystallographic system peak accumulated slip were found to be good indicators of a fatigue crack nucleation site.
► Elastic anisotropy is pivotal in polycrystal slip and observed HCF crack nucleation. ► Peak GND density coincides with experimentally observed crack nucleation site. ► Microplasticity distribution changes between first yield and multiple cycles. ► Peak accumulated slip and cyclic effective plastic strain are good FIPs. ► Crack growth path not determined by dominant slip direction.
► 3D FE implementation of continuum damage mechanics for multiaxial fatigue. ► Validation for uniaxial and notched fatigue and fretting fatigue for Ti–6Al–4V. ► Automatic incrementation scheme for ...efficient computation of damage accumulation. ► Captures effect of contact slip on fatigue life for round-on-flat fretting geometry. ► Comparisons with critical-plane multiaxial fatigue approach for fretting.
The three-dimensional finite element implementation of a continuum damage mechanics formulation for multiaxial fatigue is presented, incorporating elastic modulus reduction due to fatigue damage. The implementation is validated against theoretical and published experimental results for uniaxial and notched multiaxial fatigue under different combinations of mean and alternating stresses for Ti–6Al–4V. An automatic incrementation scheme is developed for efficient computation of damage accumulation and hence stress redistribution. The method is also implemented in two-dimensional, plane strain for fretting fatigue and is shown to successfully capture the effect of contact slip on fatigue life for a round-on-flat fretting geometry. Comparisons are also made with a critical-plane multiaxial fatigue approach for fretting. The work is a first step towards a more general fatigue damage approach to unify wear and fatigue prediction for fretting.
Regional variance in human aortic bioarchitecture responsible for the elasticity of the vessel is poorly understood. The current study quantifies the elements responsible for aortic compliance, ...namely, elastin, collagen and smooth muscle cells, using histological and stereological techniques on human tissue with a focus on regional heterogeneity. Using donated cadaveric tissue, a series of samples were excised between the proximal ascending aorta and the distal abdominal aorta, for five cadavers, each of which underwent various staining procedures to enhance specific constituents of the wall. Using polarised light microscopy techniques, the orientation of collagen fibres was studied for each location and each tunical layer of the aorta. Significant transmural and longitudinal heterogeneity in collagen fibre orientations were uncovered throughout the vessel. It is shown that a von Mises mixture model is required accurately to fit the complex collagen fibre distributions that exist along the aorta. Additionally, collagen and smooth muscle cell density was observed to increase with increasing distance from the heart, whereas elastin density decreased. Evidence clearly demonstrates that the aorta is a highly heterogeneous vessel which cannot be simplistically represented by a single compliance value. The quantification and fitting of the regional aortic bioarchitectural data, although not without its limitations, including mean cohort age of 77.6 years, facilitates the development of next‐generation finite element models that can potentially simulate the influence of regional aortic composition and microstructure on vessel biomechanics.
The microarchitecture responsible for compliance of the human aorta is quantified and shown to be highly diverse regionally. The orientation of collagen fibres is non‐symmetric and varies significantly both axially and transmurally, and the density of collagen, elastin and smooth muscle cells is also highly heterogeneous along the aortic length. The quantification of aortic bioarchitecture facilitates the development of next‐generation finite element models that can potentially simulate the influence of regional aortic composition and microstructure on vessel biomechanics.
A strain-gradient crystal plasticity framework based on physical dislocation mechanisms is developed for simulation of the experimentally observed grain size effect on the low cycle fatigue of a CoCr ...alloy. Finite-element models of the measured microstructure are presented for both as-received and heat-treated CoCr material, with significantly different grain sizes. Candidate crystallographic slip-based parameters are implemented for prediction of fatigue crack initiation. The measured beneficial effects of fine grain size on both cyclic stress–strain response and crack initiation life are predicted. The build-up of geometrically necessary dislocations as a result of strain-gradients, leading to grain-size-dependent material hardening, is shown to play a key role.
It is acceptable clinical practice to predilate a severely occluded vessel to allow better positioning of endovascular stents, and while the impact of this intervention has been examined for ...aggregate response in animals there has been no means to examine whether there are specific vessels that might benefit. Finite element methods offer the singular ability to explore the mechanical response of arteries with specific pathologic alterations in mechanics to stenting and predilation. We examined varying representations of atherosclerotic tissue including homogeneous and heterogeneous dispersion of calcified particles, and elastic, pseudo-elastic, and elastic–plastic constitutive representations of bulk atherosclerotic tissue. The constitutive representations of the bulk atherosclerotic tissue were derived from experimental test data and highlight the importance of accounting for testing mode of loading. The impact of arterial predilation is presented and, in particular, its effect on intimal predicted damage, atherosclerotic tissue von Mises and maximum principal stresses, and luminal deformation was dependent on the type of constitutive representation of diseased tissue, particularly in the presence of calcifications.
Absorbable metal stents (AMSs) are an emerging technology in the treatment of heart disease. Computational modelling of AMS performance will facilitate the development of this technology. In this ...study a physical corrosion model is developed for AMSs based on the finite element method and adaptive meshing. The model addresses a gap between currently available phenomenological corrosion models for AMSs and physical corrosion models that have been developed for more simple geometries than those of a stent. The model developed in this study captures the changing surface of a corroding three-dimensional AMS structure for the case of diffusion-controlled corrosion. Comparisons are made between model predictions and those of previously developed phenomenological corrosion models for AMSs in terms of predicted device geometry and mechanical performance during corrosion. Relationships between alloy solubility and diffusivity in the corrosion environment and device performance during corrosion are also investigated.
In this study a numerical model is developed to predict the effects of corrosion on the mechanical integrity of bioabsorbable metallic stents. To calibrate the model, the effects of corrosion on the ...integrity of biodegradable metallic foils are assessed experimentally. In addition, the effects of mechanical loading on the corrosion behaviour of the foil samples are determined. A phenomenological corrosion model is developed and applied within a finite element framework, allowing for the analysis of complex three-dimensional structures. The model is used to predict the performance of a bioabsorbable stent in an idealized arterial geometry as it is subject to corrosion over time. The effects of homogeneous and heterogeneous corrosion processes on long-term stent scaffolding ability are contrasted based on model predictions.
The implicit finite element (FE) method can encounter numerical difficulties when solving non-linear quasi-static problems. The iterative approach employed may have trouble achieving convergence in ...analyses with a highly non-linear material behaviour, such as a crystal plasticity constitutive model. In the case of the explicit FE method the solver equations can be solved directly to determine the solution without iteration, thus providing an alternative, more robust method. In this study, a rate-dependent crystal plasticity algorithm was developed for use with the explicit FE package, ABAQUS/explicit. The subroutine and an equivalent implicit version were used in a series of comparative boundary value problem analyses. The suitability of the implicit and explicit solvers to various loading conditions was assessed and multiple processor speedup rates were also investigated. The results of the study showed that, for simpler loading conditions, the implicit method had a shorter solution time. In the case of loading conditions involving contact, the explicit method proved to be the preferable choice. The explicit method displayed constantly high levels of parallelisation efficiency compared to the implicit method for analyses solved using multiple processors. In conclusion, although the implicit FE method is traditionally favoured when solving quasi-static problems, it is important to recognise the advantages that the explicit method has in solving certain loading conditions.
► A novel micromechanical fatigue crack initiation model for stents is presented. ► Importance of size-scale consistency between failure and constitutive models shown. ► Microstructural fatigue ...parameters predict realistic scatter for crack initiation. ► Conventional continuum techniques yield unrealistic scatter in life predictions. ► Crystal level kinematic hardening needed to model cyclic strain energy dissipation.
A finite element based micromechanical methodology for cyclic plasticity and fatigue crack initiation in cardiovascular stents is presented. The methodology is based on the combined use of a (global) three-dimensional continuum stent-artery model, a local micromechanical stent model, the development of a combined kinematic–isotropic hardening crystal plasticity constitutive formulation, and the application of microstructure sensitive crack initiation parameters. The methodology is applied to 316L stainless steel stents with random polycrystalline microstructures, based on scanning electron microscopy images of the grain morphology, under realistic elastic–plastic loading histories, including crimp, deployment and in vivo systolic–diastolic cyclic pressurisation. Identification of the micromechanical cyclic plasticity and failure constants is achieved via application of an objective function and a unit cell representative volume element for 316L stainless steel. Cyclic stent deformations are compared with the J2-predicted response and conventional fatigue life prediction techniques. It is shown that micromechanical fatigue analysis of stents is necessary due to the significant predicted effects of material inhomogeneity on micro-plasticity and micro-crack initiation.
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