Emulating the chondrocyte microenvironment using multi-directional mechanical stimulation in a cartilage-on-chip

Paggi, Carlo Alberto; Hendriks, Jan; Karperien, Marcel; Gac, Séverine Le

doi:10.1039/d1lc01069g

Cited by 29 publications

(14 citation statements)

References 62 publications

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“…Chondrocytes on the surface endure both compressive and shear strains, but stimulation in the deeper layers is mostly compressive. This biomechanical load causes a different elastic modulus; in the superficial zone, it is less than that in the deep zone [108,109]. Several factors should be considered to imitate the natural properties of the cartilage environment and determine the ideal setting for biomechanical stimuli to promote cartilage growth [110].…”

Section: Factors Affecting Cellular Responses On Biomechanical Stimul...mentioning

confidence: 99%

Progress in biomechanical stimuli on the cell-encapsulated hydrogels for cartilage tissue regeneration

Taheri

Ghazali

et al. 2023

Biomater Res

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Background Worldwide, many people suffer from knee injuries and articular cartilage damage every year, which causes pain and reduces productivity, life quality, and daily routines. Medication is currently primarily used to relieve symptoms and not to ameliorate cartilage degeneration. As the natural healing capacity of cartilage damage is limited due to a lack of vascularization, common surgical methods are used to repair cartilage tissue, but they cannot prevent massive damage followed by injury. Main body Functional tissue engineering has recently attracted attention for the repair of cartilage damage using a combination of cells, scaffolds (constructs), biochemical factors, and biomechanical stimuli. As cyclic biomechanical loading is the key factor in maintaining the chondrocyte phenotype, many studies have evaluated the effect of biomechanical stimulation on chondrogenesis. The characteristics of hydrogels, such as their mechanical properties, water content, and cell encapsulation, make them ideal for tissue-engineered scaffolds. Induced cell signaling (biochemical and biomechanical factors) and encapsulation of cells in hydrogels as a construct are discussed for biomechanical stimulation-based tissue regeneration, and several notable studies on the effect of biomechanical stimulation on encapsulated cells within hydrogels are discussed for cartilage regeneration. Conclusion Induction of biochemical and biomechanical signaling on the encapsulated cells in hydrogels are important factors for biomechanical stimulation-based cartilage regeneration.

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Section: Factors Affecting Cellular Responses On Biomechanical Stimul...mentioning

confidence: 99%

Progress in biomechanical stimuli on the cell-encapsulated hydrogels for cartilage tissue regeneration

Taheri

Ghazali

et al. 2023

Biomater Res

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“…due to the alignment of contractile muscle cells [25]. Beyond simple measurements, the device can also be filled with hydrogels in order to guide the differentiation of cells within the spheroids, as was elegantly demonstrated recently [26].…”

Section: Discussion and Outlookmentioning

confidence: 99%

Using a micro-device with a deformable ceiling to probe stiffness heterogeneities within 3D cell aggregates

Jain,

Belkadi,

Michaut

et al. 2023

Preprint

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Recent advances in the field of mechanobiology have led to the development of methods to characterize single-cell or monolayer mechanical properties and link them to their functional behaviour. However, there remains a strong need to establish this link for three-dimensional multicellular aggregates, which better mimic tissue function. Here we present a platform to actuate and observe many such aggregates within one deformable micro-device. The platform consists of a single PDMS piece cast on a 3D-printed mold and bonded to a glass slide or coverslip. It consists of a chamber containing cell spheroids, which is adjacent to air cavities that are fluidically independent. Controlling the air pressure in these air cavities leads to a vertical displacement of the chamber’s ceiling. The device can be used in static or dynamic modes over time-scales of seconds to hours, with displacement amplitudes from a few μm to several tens of microns. Further, we show how the compression protocols can be used to obtain measurements of stiffness heterogeneities within individual co-culture spheroids, by comparing image correlations of spheroids at different levels of compression with finite element simulations. The labeling of the cells and their cytoskeleton is combined with image correlation methods to relate the structure of the co-culture spheroid with its mechanical properties at different locations. The device is compatible with various microscopy techniques, including confocal microscopy, which can be used to observe the displacements and rearrangements of single cells and neighborhoods within the aggregate. The complete experimental and imaging platform can now be used to provide multi-scale measurements that link single-cell behavior with the global mechanical response of the aggregates.

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“…[315][316][317][318] The difference between these devices and other traditional cell platforms is that they can be used for biochemical, mechanical, and electrical stimulations. [319,320] Besides, OoCs can substitute animal models and markedly reduce experiments' time and cost. [321] Other OoCs' benefits are the capability to recover exit fluids, realtime screening of drugs, live imaging, and disease modeling, to name but a few.…”

Section: Development Of Cartilage-related Organ-on-chipsmentioning

confidence: 99%

Progress of Microfluidic Hydrogel‐Based Scaffolds and Organ‐on‐Chips for the Cartilage Tissue Engineering

et al. 2023

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Cartilage degeneration is among the fundamental reasons behind disability and pain across the globe. Numerous approaches have been employed to treat cartilage diseases. Nevertheless, none have shown acceptable outcomes in the long run. In this regard, the convergence of tissue engineering and microfabrication principles can allow developing more advanced microfluidic technologies, thus offering attractive alternatives to current treatments and traditional constructs used in tissue engineering applications. Herein, the current developments involving microfluidic hydrogel‐based scaffolds, promising structures for cartilage regeneration, ranging from hydrogels with microfluidic channels to hydrogels prepared by the microfluidic devices, that enable therapeutic delivery of cells, drugs, and growth factors, as well as cartilage‐related organ‐on‐chips are reviewed. Thereafter, cartilage anatomy and types of damages, and present treatment options are briefly overviewed. Various hydrogels are introduced, and the advantages of microfluidic hydrogel‐based scaffolds over traditional hydrogels are thoroughly discussed. Furthermore, available technologies for fabricating microfluidic hydrogel‐based scaffolds and microfluidic chips are presented. The preclinical and clinical applications of microfluidic hydrogel‐based scaffolds in cartilage regeneration and the development of cartilage‐related microfluidic chips over time are further explained. The current developments, recent key challenges, and attractive prospects that should be considered so as to develop microfluidic systems in cartilage repair are highlighted.

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Emulating the chondrocyte microenvironment using multi-directional mechanical stimulation in a cartilage-on-chip

Abstract: The multi-directional mechanical stimulation experienced by cartilage during motion is transferred to chondrocytes, which respond by releasing matrix proteins and/or matrix-degrading enzymes.

Cited by 29 publications

References 62 publications

Progress in biomechanical stimuli on the cell-encapsulated hydrogels for cartilage tissue regeneration

Progress in biomechanical stimuli on the cell-encapsulated hydrogels for cartilage tissue regeneration

Using a micro-device with a deformable ceiling to probe stiffness heterogeneities within 3D cell aggregates

Progress of Microfluidic Hydrogel‐Based Scaffolds and Organ‐on‐Chips for the Cartilage Tissue Engineering

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