68 research outputs found
A combined experimental and modelling approach to aortic valve viscoelasticity in tensile deformation
No full textThe quasi-static mechanical behaviour of the aortic valve (AV) is highly non-linear and anisotropic in nature and reflects the complex collagen fibre kinematics in response to applied loading. However, little is known about the viscoelastic behaviour of the AV. The aim of this study was to investigate porcine AV tissue under uniaxial tensile deformation, in order to establish the directional dependence of its viscoelastic behaviour. Rate dependency associated with different mechanical properties was investigated, and a new viscoelastic model incorporating rate effects developed, based on the Kelvin-Voigt model. Even at low applied loads, experimental results showed rate dependency in the stress-strain response, and also hysteresis and dissipation effects. Furthermore, corresponding values of each parameter depended on the loading direction. The model successfully predicted the experimental data and indicated a 'shear-thinning' behaviour. By extrapolating the experimental data to that at physiological strain rates, the model predicts viscous damping coefficients of 8.3 MPa s and 3.9 MPa s, in circumferential and radial directions, respectively. This implies that the native AV offers minimal resistance to internal shear forces induced by blood flow, a potentially critical design feature for substitute implants. These data suggest that the mechanical behaviour of the AV cannot be thoroughly characterised by elastic deformation and fibre recruitment assumptions alon
On the specimen length dependency of tensile mechanical properties in soft tissues: gripping effects and the characteristic decay length
No full textEngineering growth factor gradients to drive spatiotemporal tissue patterning in organ-on-a-chip systems
No full textSpatial heterogeneity plays a key role in the development and function of human tissues and therefore needs to be incorporated within in vitro models to maximise physiological relevance and predictive power. Here, we developed and optimised methods to generate spatial heterogeneity of hydrogel-embedded bioactive signalling molecules within organ-on-a-chip (OOAC) systems, to drive spatiotemporal tissue patterning through controlled stem cell differentiation. As an exemplar application, we spatially patterned bone morphogenetic protein-2 (BMP-2) in both closed-channel and open-chamber OOAC formats. The resulting BMP-2 gradient in 3D heparin methacryloyl/gelatin methacryloyl, successfully drove spatially divergent differentiation of human bone marrow-derived stem cells into bone-like and cartilage-like regions, mimicking the process of endochondral ossification in the growth plate. The application of hydrogel-embedded morphogens to drive spatial tissue patterning within OOAC systems represents a significant technological advancement and has broad-ranging applicability for a diverse range of tissues and organs, and a wide variety of OOAC platforms
Anisotropic time-dependant behaviour of the aortic valve
No full textThe complex tri-layered structure of the aortic valve (AV) results in anisotropic quasi–static mechanical behaviour. However, its influence on AV viscoelasticity remains poorly understood. Viscoelasticity may strongly influence AV dynamic mechanical behaviour, making it essential to characterise the time-dependent response for designing successful substitutes. This study attempts to characterise the time-dependent behaviour of the AV at different strain and load increments, and to gain insight into the contribution of the microstructure to this behaviour. Uniaxial incremental stress-relaxation and creep experiments were undertaken, and the experimental data analysed with a generalised Maxwell model, to determine the characteristic time-dependent parameters. Results showed that the time dependent response of the tissue differed with the loading direction, and also with the level of applied load or strain, in both stress-relaxation and creep phenomena. Both phenomena were consistently more pronounced in the radial loading direction. Fitting of the Maxwell model highlighted that the time dependent modes required to model the data also varied in different increments, and additionally with the loading direction. These results suggest that different micro-structural mechanisms may be activated in stress-relaxation and creep, determined by the microstructural organisation of the valve matrix in each loading direction, at each strain or load increment.<br/
Advanced glycation end-products reduce collagen molecular sliding to affect collagen fibril damage mechanisms but not stiffness
No full textAdvanced glycation end-products (AGE) contribute to age-related connective tissue damage and functional deficit. The documented association between AGE formation on collagens and the correlated progressive stiffening of tissues has widely been presumed causative, despite the lack of mechanistic understanding. The present study investigates precisely how AGEs affect mechanical function of the collagen fibril – the supramolecular functional load-bearing unit within most tissues. We employed synchrotron small-angle X-ray scattering (SAXS) and carefully controlled mechanical testing after introducing AGEs in explants of rat-tail tendon using the metabolite methylglyoxal (MGO). Mass spectrometry and collagen fluorescence verified substantial formation of AGEs by the treatment. Associated mechanical changes of the tissue (increased stiffness and failure strength, decreased stress relaxation) were consistent with reports from the literature. SAXS analysis revealed clear changes in molecular deformation within MGO treated fibrils. Underlying the associated increase in tissue strength, we infer from the data that MGO modified collagen fibrils supported higher loads to failure by maintaining an intact quarter-staggered conformation to nearly twice the level of fibril strain in controls. This apparent increase in fibril failure resistance was characterized by reduced side-by-side sliding of collagen molecules within fibrils, reflecting lateral molecular interconnectivity by AGEs. Surprisingly, no change in maximum fibril modulus (2.5 GPa) accompanied the changes in fibril failure behavior, strongly contradicting the widespread assumption that tissue stiffening in ageing and diabetes is directly related to AGE increased fibril stiffness. We conclude that AGEs can alter physiologically relevant failure behavior of collagen fibrils, but that tissue level changes in stiffness likely occur at higher levels of tissue architecture
Specimen dimensions influence the measurement of material properties in tendon fascicles
No full textStress, strain and modulus are regularly used to characterize material properties of tissue samples. However, when comparing results from different studies it is evident the reported material properties, particularly failure strains, vary hugely. The aim of our study was to characterize how and why specimen length and cross-sectional area (CSA) appear to influence failure stress, strain and modulus in fascicles from two functionally different tendons. Fascicles were dissected from five rat tails and five bovine foot extensors, their diameters determined by a laser micrometer, and loaded to failure at a range of grip-to-grip lengths. Strain to failure significantly decreased with increasing in specimen length in both rat and bovine fascicles, while modulus increased. Specimen length did not influence failure stress in rat tail fascicles, although in bovine fascicles it was significantly lower in the longer 40 mm specimens compared to 5 and 10 mm specimens. The variations in failure strain and modulus with sample length could be predominantly explained by end-effects. However, it was also evident that strain fields along the sample length were highly variable and notably larger towards the ends of the sample than the mid-section even at distances in excess of 5 mm from the gripping points. Failure strain, stress and modulus correlated significantly with CSA at certain specimen lengths. Our findings have implications for the mechanical testing of tendon tissue: while it is not always possible to control for fascicle length and/or CSA, these parameters have to be taken into account when comparing samples of different dimensions
GAG depletion increases the stress relaxation response of tendon fascicles, but does not influence recovery
No full textCyclic and static loading regimes are commonly used to study tenocyte metabolism in vitro and to improve our understanding of exercise-associated tendon pathologies. The aims of our study were to investigate if cyclic and static stress relaxation affected the mechanical properties of tendon fascicles differently, if this effect was reversible after a recovery period, and if the removal of glycosaminoglycans (GAGs) affected sample recovery. Tendon fascicles were dissected frombovine-foot extensors and subjected to 14% cyclic (1 Hz) or static tensile strain for 30 min. Additional fascicles were incubated overnight in buffer with 0.5 U chondroitinase ABC or in buffer alone prior to the static stress-relaxation regime. To assess the effect of different stress-relaxation regimes, a quasi-static test to failure was carried out, either directly post loading or after a 2 h recovery period, and compared with unloaded control fascicles. Both stress-relaxation regimes led to a significant reduction in fascicle failure stress and strain, but this was more pronounced in the cyclically loaded specimens. Removal of GAGs led to more stress relaxation and greater reductions in failure stress after static loading compared to controls. The reduction in mechanical properties was partially reversible in all samples, given a recovery period of 2 h. This has implications for mechanical testing protocols, as a time delay between fatiguing specimens and characterization of mechanical properties will affect the results. GAGs appear to protect tendon fascicles from fatigue effects, possibly by enabling sample hydration
Structure and collagen crimp patterns of functionally distinct equine tendons, revealed by quantitative polarised light microscopy (qPLM)
No full textStructure-function relationships in tendons are directly influenced by the arrangement of collagen fibres. However, the details of such arrangements in functionally distinct tendons remain obscure. This study demonstrates the use of quantitative polarised light microscopy (qPLM) to identify structural differences in two major tendon compartments at the mesoscale: fascicles and interfascicular matrix (IFM). It contrasts functionally distinct positional and energy storing tendons, and considers changes with age. Of particular note, the technique facilitates the analysis of crimp parameters, in which cutting direction artefact can be accounted for and eliminated, enabling the first detailed analysis of crimp parameters across functionally distinct tendons.
IFM shows lower birefringence (0.0013 ± 0.0001 [-]), as compared to fascicles (0.0044 ± 0.0005 [-]), indicating that the volume fraction of fibres must be substantially lower in the IFM. Interestingly, no evidence of distinct fibre directional dispersions between equine energy storing superficial digital flexor tendons (SDFTs) and positional common digital extensor tendons (CDETs) were noted, suggesting either more subtle structural differences between tendon types or changes focused in the non-collagenous components.
By contrast, collagen crimp characteristics are strongly tendon type specific, indicating crimp specialisation is crucial in the respective mechanical function. SDFTs showed much finer crimp (21.1 ± 5.5 µm) than positional CDETs (135.4 ± 20.1 µm). Further, tendon crimp was finer in injured tendon, as compared to its healthy equivalents. Crimp angle differed strongly between tendon types as well, with average of 6.5 ± 1.4° in SDFTs and 13.1 ± 2.0° in CDETs, highlighting a substantially tighter crimp in the SDFT, likely contributing to its effective recoil capacity
Zonal variation in primary cilia elongation correlates with localized biomechanical degradation in stress deprived tendon
No full textEPSRC; Institute of Bioengineering at QMU
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