Guide to mechanical characterization of articular cartilage and hydrogel constructs based on a systematic in silico parameter sensitivity analysis

Elahi, Seyed Ali; Tanska, Petri; Mukherjee, Satanik; Korhonen, Rami K.; Geris, Liesbet; Jonkers, Ilse; Famaey, Nele

doi:10.1016/j.jmbbm.2021.104795

Cited by 8 publications

(7 citation statements)

References 44 publications

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“…To model the mechanical behavior of articular cartilage, a 3D FRPE material model was used (38). The FE models were implemented with sample-specific depth-dependent fibril orientation using data from PLM measurements ( Fig.…”

Section: Methodsmentioning

confidence: 99%

Mechanical Drivers of Glycosaminoglycan Content Changes in Intact and Damaged Human Cartilage

Elahi,

Castro-Viñuelas,

Tanska

et al. 2024

Preprint

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Articular cartilage undergoes significant degeneration during osteoarthritis, currently lacking effective treatments. This study explores mechanical influences on cartilage health using a novel finite element-based mechanoregulatory model, predicting combined degenerative and regenerative responses to mechanical loading. Calibrated and validated through one-week longitudinal ex vivo experiments on intact and damaged cartilage samples, the model underscores the roles of maximum shear strain, fluid velocity, and dissipated energy in driving changes in cartilage glycosaminoglycan (GAG) content. It delineates the distinct regenerative contributions of fluid velocity and dissipated energy, alongside the degenerative contribution of maximum shear strain, to GAG adaptation in both intact and damaged cartilage under physiological mechanical loading. Remarkably, the model predicts increased GAG production even in damaged cartilage, consistent with our in vitro experimental findings. Beyond advancing our understanding of mechanical loading’s role in cartilage homeostasis, our model aligns with contemporary ambitions by exploring the potential of in silico trials to optimize mechanical loading in degenerative joint disease, fostering personalized rehabilitation.

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Section: Methodsmentioning

confidence: 99%

Mechanical Drivers of Glycosaminoglycan Content Changes in Intact and Damaged Human Cartilage

Elahi,

Castro-Viñuelas,

Tanska

et al. 2024

Preprint

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“…This was crucial for applying a strain-controlled unconfined compression to the sample using a mechanical loading setup (Bose ElectroForce, TA Instrument Company). Our unconfined compression loading protocol comprised of a 20% applied strain at a rate of 1% per second adjusted to the measured height of each individual sample, followed by 15 minutes of relaxation 61,62 . The reaction force was recorded during the compression-relaxation experiment.…”

Section: Methodsmentioning

confidence: 99%

“…To obtain the mechanical properties of the hydrogels, an inverse finite element (FE)-based mechanical characterization approach was implemented. To this end, an FE simulation of the unconfined compression tests for each sample was created in Abaqus using a poro-hyperelastic material model as previously reported 62 . Briefly, the gels were simulated using 2D axisymmetric models and the material model consists of a Neo-Hookean solid matrix and a fluid phase.…”

Section: Methodsmentioning

confidence: 99%

Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth

Shapeti,

Barrasa-Fano,

Fattah

et al. 2023

Preprint

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Force-driven cellular interactions are known to play a critical role in cancer cell invasion, but have remained largely unexplored in the context of vascular abnormalities, partly due to a lack of suitable genetic and cellular models. One such vascular abnormality, cerebral cavernous malformation (CCM) is characterized by leaky, tumor-like vessels in the brain, where CCM mutant cells recruit wild-type cells from the surrounding endothelium to form mosaic lesions and promote lesion growth; however the mechanisms underlying this recruitment remain poorly understood. Here, we use 3D traction force microscopy in a in-vitro model of early angiogenic invasion to reveal that hyper-angiogenic CCM2-silenced endothelial cells enhance angiogenic invasion of neighboring wild-type cells through force and extracellular matrix-guided mechanisms. We show that mechanically hyperactive CCM2-silenced tips guide wild-type cells by exerting and transmitting pulling forces and by leaving degraded paths in the matrix as cues promoting invasion in a ROCKs-dependent manner. This transmission of forces is associated with a reinforcement of β1 integrin-dependent adhesive sites and actin cytoskeleton in the wild-type followers. We also show that during this process wild-type cells are reprogrammed into stalk cells through activation of matrisome and DNA replication programs, eventually leading to cell proliferation. These observations unveil a novel vascular lesion growth mechanism where CCM2 mutants hijack the function of wild-type cells to fuel CCM lesion growth. By integrating biophysical computational methodologies to quantify cellular forces with advanced molecular techniques, we provide new insights in the etiology of vascular malformations, and open up avenues to study the role of cell mechanics in tissue heterogeneity and disease progression.

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“…At low temperature, a small amount of relaxation, around 40%, is observed and after 900 s a plateau is observed for both hydrogels (Figure S6). This relaxation behavior is attributed to the fluid pressure which relaxes over time [59]. Modulus (kPa) S7.…”

Section: Mechanical Properties: Compression-relaxationmentioning

confidence: 99%

A Spontaneous In Situ Thiol-Ene Crosslinking Hydrogel with Thermo-Responsive Mechanical Properties

Aerts,

Vovchenko,

Elahi

et al. 2024

Polymers

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The thermo-responsive behavior of Poly(N-isopropylacrylamide) makes it an ideal candidate to easily embed cells and allows the polymer mixture to be injected. However, P(NiPAAm) hydrogels possess minor mechanical properties. To increase the mechanical properties, a covalent bond is introduced into the P(NIPAAm) network through a biocompatible thiol-ene click-reaction by mixing two polymer solutions. Co-polymers with variable thiol or acrylate groups to thermo-responsive co-monomer ratios, ranging from 1% to 10%, were synthesized. Precise control of the crosslink density allowed customization of the hydrogel’s mechanical properties to match different tissue stiffness levels. Increasing the temperature of the hydrogel above its transition temperature of 31 °C induced the formation of additional physical interactions. These additional interactions both further increased the stiffness of the material and impacted its relaxation behavior. The developed optimized hydrogels reach stiffnesses more than ten times higher compared to the state of the art using similar polymers. Furthermore, when adding cells to the precursor polymer solutions, homogeneous thermo-responsive hydrogels with good cell viability were created upon mixing. In future work, the influence of the mechanical micro-environment on the cell’s behavior can be studied in vitro in a continuous manner by changing the incubation temperature.

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Guide to mechanical characterization of articular cartilage and hydrogel constructs based on a systematic in silico parameter sensitivity analysis

Cited by 8 publications

References 44 publications

Mechanical Drivers of Glycosaminoglycan Content Changes in Intact and Damaged Human Cartilage

Mechanical Drivers of Glycosaminoglycan Content Changes in Intact and Damaged Human Cartilage

Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth

A Spontaneous In Situ Thiol-Ene Crosslinking Hydrogel with Thermo-Responsive Mechanical Properties

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