It has been previously demonstrated that mechanical stimuli are important for multipotent human bone marrow-derived mesenchymal stromal cells (hMSCs) to maintain good tissue homeostasis and even to enhance tissue repair processes. In tendons, this is achieved by promoting the cellular proliferation and tenogenic expression/differentiation. The present study was conducted to determine the optimal loading conditions needed to achieve the best proliferation rates and tenogenic differentiation potential. The effects of mechanical uniaxial stretching using different rates and strains were performed on hMSCs cultured in vitro. hMSCs were subjected to cyclical uniaxial stretching of 4, 8 or 12 % strain at 0.5 or 1 Hz for 6, 24, 48 or 72 h. Cell proliferation was analyzed using alamarBlue[Formula: see text] assay, while hMSCs differentiation was analyzed using total collagen assay and specific tenogenic gene expression markers (type I collagen, type III collagen, decorin, tenascin-C, scleraxis and tenomodulin). Our results demonstrate that the highest cell proliferation is observed when 4 % strain [Formula: see text] 1 Hz was applied. However, at 8 % strain [Formula: see text] 1 Hz loading, collagen production and the tenogenic gene expression were highest. Increasing strain or rates thereafter did not demonstrate any significant increase in both cell proliferation and tenogenic differentiation. In conclusion, our results suggest that 4 % [Formula: see text] 1 Hz cyclic uniaxial loading increases cell proliferation, but higher strains are required for superior tenogenic expressions. This study suggests that selected loading regimes will stimulate tenogenesis of hMSCs.
Experimental findings indicate that in-situ chondrocytes die readily following impact loading, but remain essentially unaffected at low (non-impact) strain rates. This study was aimed at identifying possible causes for cell death in impact loading by quantifying chondrocyte mechanics when cartilage was subjected to a 5% nominal tissue strain at different strain rates. Multi-scale modelling techniques were used to simulate cartilage tissue and the corresponding chondrocytes residing in the tissue. Chondrocytes were modelled by accounting for the cell membrane, pericellular matrix and pericellular capsule. The results suggest that cell deformations, cell fluid pressures and fluid flow velocity through cells are highest at the highest (impact) strain rate, but they do not reach damaging levels. Tangential strain rates of the cell membrane were highest at the highest strain rate and were observed primarily in superficial tissue cells. Since cell death following impact loading occurs primarily in superficial zone cells, we speculate that cell death in impact loading is caused by the high tangential strain rates in the membrane of superficial zone cells causing membrane rupture and loss of cell content and integrity.
The healing process of ruptured tendons is problematic due to scar tissue formation and deteriorated material properties, and in some cases, it may take nearly a year to complete. Mechanical loading has been shown to positively influence tendon healing; however, the mechanisms remain unclear. Computational mechanobiology methods employed extensively to model bone healing have achieved high fidelity. This study aimed to investigate whether an established hyperelastic fibre-reinforced continuum model introduced by Gasser, Ogden and Holzapfel (GOH) can be used to capture the mechanical behaviour of the Achilles tendon under loading during discrete timepoints of the healing process and to assess the model's sensitivity to its microstructural parameters. Curve fitting of the GOH model against experimental tensile testing data of rat Achilles tendons at four timepoints during the tendon repair was used and achieved excellent fits ([Formula: see text]). A parametric sensitivity study using a three-level central composite design, which is a fractional factorial design method, showed that the collagen-fibre-related parameters in the GOH model-[Formula: see text] and [Formula: see text]-had almost equal influence on the fitting. This study demonstrates that the GOH hyperelastic fibre-reinforced model is capable of describing the mechanical behaviour of healing tendons and that further experiments should focus on establishing the structural and material parameters of collagen fibres in the healing tissue.
This study employs a computational approach to analyse the impact of morphological changes on the structural properties of biodegradable porous Mg subjected to a dynamic immersion test for its application as a bone scaffold. Porous Mg was immersed in a dynamic immersion test for 24, 48, and 72 h. Twelve specimens were prepared and scanned using micro-CT and then reconstructed into a 3D model for finite element analysis. The structural properties from the numerical simulation were then compared to the experimental values. Correlations between morphological parameters, structural properties, and fracture type were then made. The relative losses were observed to be in agreement with relative mass loss done experimentally. The degradation rates determined using exact (degraded) surface area at particular immersion times were on average 20% higher than the degradation rates obtained using original surface area. The dynamic degradation has significantly impacted the morphological changes of porous Mg in volume fraction, surface area, and trabecular separation, which in turn affects its structural properties and increases the immersion time.
The present study has sought to investigate the fluid characteristic and mechanical properties of trabecular bone using fluid-structure interaction (FSI) approach under different trabecular bone orientations. This method imposed on trabecular bone structure at both longitudinal and transverse orientations to identify effects on shear stress, permeability, stiffness and stress regarded to the trabeculae. Sixteen FSI models were performed on different range trabecular cubes of 27 mm3 with eight models developed for each longitudinal and transverse direction. Results show that there was a moderate correlation between permeability and porosity, and surface area in the longitudinal and transverse orientations. For the longitudinal orientation, the permeability values varied between 3.66 × 10-8 and 1.9 × 10-7 and the sheer stress values varied between 0.05 and 1.8 Pa, whilst for the transverse orientation, the permeability values varied between 5.95 × 10-10 and 1.78 × 10-8 and the shear stress values varied between 0.04 and 3.1 Pa. Here, transverse orientation limits the fluid flow from passing through the trabeculae due to high shear stress disturbance generated within the trabecular bone region. Compared to physiological loading direction (longitudinal orientation), permeability is higher within the range known to trigger a response in bone cells. Additionally, shear stresses also increase with bone surface area. This study suggests the shear stress within bone marrow in real trabecular architecture could provide the mechanical signal to marrow cells that leads to bone anabolism and can depend on trabecular orientation.
The geometric control of bone tissue growth plays a significant role in bone remodelling, age-related bone loss, and tissue engineering. However, how exactly geometry influences the behaviour of bone-forming cells remains elusive. Geometry modulates cell populations collectively through the evolving space available to the cells, but it may also modulate the individual behaviours of cells. To factor out the collective influence of geometry and gain access to the geometric regulation of individual cell behaviours, we develop a mathematical model of the infilling of cortical bone pores and use it with available experimental data on cortical infilling rates. Testing different possible modes of geometric controls of individual cell behaviours consistent with the experimental data, we find that efficient smoothing of irregular pores only occurs when cell secretory rate is controlled by porosity rather than curvature. This porosity control suggests the convergence of a large scale of intercellular signalling to single bone-forming cells, consistent with that provided by the osteocyte network in response to mechanical stimulus. After validating the mathematical model with the histological record of a real cortical pore infilling, we explore the infilling of a population of randomly generated initial pore shapes. We find that amongst all the geometric regulations considered, the collective influence of curvature on cell crowding is a dominant factor for how fast cortical bone pores infill, and we suggest that the irregularity of cement lines thereby explains some of the variability in double labelling data as well as the overall speed of osteon infilling.
The first carpometacarpal (CMC) joint, located at the base of the thumb and formed by the junction between the first metacarpal and trapezium, is a common site for osteoarthritis of the hand. The shape of both the first metacarpal and trapezium contributes to the intrinsic bony stability of the joint, and variability in the morphology of both these bones can affect the joint's function. The objectives of this study were to quantify the morphological variation in the complete metacarpal and trapezium and determine any correlation between anatomical features of these two components of the first CMC joint. A multi-object statistical shape modelling pipeline, consisting of scaling, hierarchical rigid registration, non-rigid registration and projection pursuit principal component analysis, was implemented. Four anatomical measures were quantified from the shape model, namely the first metacarpal articular tilt and torsion angles and the trapezium length and width. Variations in the first metacarpal articular tilt angle (- 6.3°
False lumen thrombosis (FLT) in type B aortic dissection has been associated with the progression of dissection and treatment outcome. Existing computational models mostly assume rigid wall behavior which ignores the effect of flap motion on flow and thrombus formation within the FL. In this study, we have combined a fully coupled fluid-structure interaction (FSI) approach with a shear-driven thrombosis model described by a series of convection-diffusion reaction equations. The integrated FSI-thrombosis model has been applied to an idealized dissection geometry to investigate the interaction between vessel wall motion and growing thrombus. Our simulation results show that wall compliance and flap motion can influence the progression of FLT. The main difference between the rigid and FSI models is the continuous development of vortices near the tears caused by drastic flap motion up to 4.45 mm. Flap-induced high shear stress and shear rates around tears help to transport activated platelets further to the neighboring region, thus speeding up thrombus formation during the accelerated phase in the FSI models. Reducing flap mobility by increasing the Young's modulus of the flap slows down the thrombus growth. Compared to the rigid model, the predicted thrombus volume is 25% larger using the FSI-thrombosis model with a relatively mobile flap. Furthermore, our FSI-thrombosis model can capture the gradual effect of thrombus growth on the flow field, leading to flow obstruction in the FL, increased blood viscosity and reduced flap motion. This model is a step closer toward simulating realistic thrombus growth in aortic dissection, by taking into account the effect of intimal flap and vessel wall motion.