Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

Erdemir, Ahmet; Bennetts, Craig; Davis, Sean; Reddy, Akhil; Sibole, Scott C.

doi:10.1098/rsfs.2014.0081

Cited by 24 publications

(25 citation statements)

References 52 publications

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“…Thus, the contours of strain distribution were compared with those obtained from high-throughput multiscale 3D models of chondrocytes, with at most differences of 2.5% [18], to ensure validity of the results of subsequent analysis.…”

Section: Discussionmentioning

confidence: 99%

Study of the Mechanical Environment of Chondrocytes in Articular Cartilage Defects Repaired Area under Cyclic Compressive Loading

Liu

Duan

Zhang

et al. 2017

Journal of Healthcare Engineering

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COMSOL finite element software was used to establish a solid-liquid coupling biphasic model of articular cartilage and a microscopic model of chondrocytes, using modeling to take into account the shape and number of chondrocytes in cartilage lacuna in each layer. The effects of cyclic loading at different frequencies on the micromechanical environment of chondrocytes in different regions of the cartilage were studied. The results showed that low frequency loading can cause stress concentration of superficial chondrocytes. Moreover, along with increased frequency, the maximum value of stress response curve of chondrocytes decreased, while the minimum value increased. When the frequency was greater than 0.2 Hz, the extreme value stress of response curve tended to be constant. Cyclic loading had a large influence on the distribution of liquid pressure in chondrocytes in the middle and deep layers. The concentration of fluid pressure changed alternately from intracellular to peripheral in the middle layer. Both the range of liquid pressure in the upper chondrocytes and the maximum value of liquid pressure in the lower chondrocytes in the same lacunae varied greatly in the deep layer. At the same loading frequency, the elastic modulus of artificial cartilage had little effect on the mechanical environment of chondrocytes.

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Section: Discussionmentioning

confidence: 99%

Study of the Mechanical Environment of Chondrocytes in Articular Cartilage Defects Repaired Area under Cyclic Compressive Loading

Liu

Duan

Zhang

et al. 2017

Journal of Healthcare Engineering

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“…The use of animal models adds a layer of complexity to this problem and appropriate regard must be given to the spatial and temporal differences in these models. Figure developed from concepts described in refs 3, 21, 61, 63…”

Section: Biology As a Systemmentioning

confidence: 99%

“…OA may also be considered a disorder of mechanotransduction given that forces on the joint are integral to the health of the cartilage69 and evidence that OA and aged chondrocytes have altered mechanical properties 70, 71, 72. Biomechanical signals are also multiscale responding to age and disease, Figure 3, with effects at a tissue level (differential loading across joint, load sharing across particular tissues), within a tissue (differential compression on zonal regions of cartilage) and cell‐associated (mechanotransduction through the pericellular matrix of the chondron) 61. Critically, there is not a single mechanical signal that transduces into an electrical or chemical signal intracellularly and different forces require a level of integration (compression, osmolarity, fluid shear, hydrostatic pressures); the contribution of each still needs to be defined 73.…”

Section: Biology As a Systemmentioning

confidence: 99%

Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies

Mueller

Peffers

Proctor³

et al. 2017

J. Orthop. Res.

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Systems orientated research offers the possibility of identifying novel therapeutic targets and relevant diagnostic markers for complex diseases such as osteoarthritis. This review demonstrates that the osteoarthritis research community has been slow to incorporate systems orientated approaches into research studies, although a number of key studies reveal novel insights into the regulatory mechanisms that contribute both to joint tissue homeostasis and its dysfunction. The review introduces both top‐down and bottom‐up approaches employed in the study of osteoarthritis. A holistic and multiscale approach, where clinical measurements may predict dysregulation and progression of joint degeneration, should be a key objective in future research. The review concludes with suggestions for further research and emerging trends not least of which is the coupled development of diagnostic tests and therapeutics as part of a concerted effort by the osteoarthritis research community to meet clinical needs. © 2017 The Authors. Journal of Orthopaedic Research Published by Wiley Periodicals, Inc. on behalf of Orthopaedic Research Society. J Orthop Res 35:1573–1588, 2017.

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“…Computational research has thoroughly investigated how continuum mechanics, molecular mechanics, or a combination of both can explain the multiscale force transfer and downstream chemical pathway activation in soft tissues (e.g. skeletal muscle 6–8 , cardiovascular system 9,10 and articular cartilage 11,12 ). Experimental paradigms have used isolated single cell mechanics, tissue equivalents, or in situ studies to probe multiscale strain transfer and mechanotransduction mechanisms in the ECM, cell, and nucleus 13,14 .…”

Section: Introductionmentioning

confidence: 99%

In Vivo Multiscale and Spatially-Dependent Biomechanics Reveals Differential Strain Transfer Hierarchy in Skeletal Muscle

Ghosh

Cimino

Scott

et al. 2017

ACS Biomater. Sci. Eng.

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Biological tissues have a complex hierarchical architecture that spans organ to subcellular scales and comprises interconnected biophysical and biochemical machinery. Mechanotransduction, gene regulation, gene protection, and structure-function relationships in tissues depend on how force and strain are modulated from macro to micro scales, and vice versa. Traditionally, computational and experimental techniques have been used in common model systems (e.g., embryos) and simple strain measures were applied. But the hierarchical transfer of mechanical parameters like strain in mammalian systems is largely unexplored in vivo. Here, we experimentally probed complex strain transfer processes in mammalian skeletal muscle tissue over multiple biological scales using complementary in vivo ultrasound and optical imaging approaches. An iterative hyperelastic warping technique quantified the spatially-dependent strain distributions in tissue, matrix, and subcellular (nuclear) structures, and revealed a surprising increase in strain magnitude and heterogeneity in active muscle as the spatial scale also increased. The multiscale strain heterogeneity indicates tight regulation of mechanical signals to the nuclei of individual cells in active muscle, and an emergent behavior appearing at larger (e.g. tissue) scales characterized by dramatically increased strain complexity.

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Multiscale cartilage biomechanics: technical challenges in realizing a high-throughput modelling and simulation workflow

Abstract: One contribution of 11 to a theme issue 'Multiscale modelling in biomechanics: theoretical, computational and translational challenges'.

Cited by 24 publications

References 52 publications

Study of the Mechanical Environment of Chondrocytes in Articular Cartilage Defects Repaired Area under Cyclic Compressive Loading

Study of the Mechanical Environment of Chondrocytes in Articular Cartilage Defects Repaired Area under Cyclic Compressive Loading

Systems approaches in osteoarthritis: Identifying routes to novel diagnostic and therapeutic strategies

In Vivo Multiscale and Spatially-Dependent Biomechanics Reveals Differential Strain Transfer Hierarchy in Skeletal Muscle

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