Simultaneous anabolic and catabolic responses of human chondrocytes seeded in collagen hydrogels to long-term continuous dynamic compression

Nebelung, Sven; Gavénis, Karsten; Lüring, C.; Zhou, Beixian; Mueller-Rath, Ralf; Stoffel, Marcus; Tingart, Markus; Rath, Björn

doi:10.1016/j.aanat.2011.12.008

Cited by 35 publications

(39 citation statements)

References 42 publications

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“…Additionally, exogenous loading can alter Superficial Zone Protein expression (Neu, Khalafi et al 2007), induce transcription of ECM genes (Bougault, Paumier et al 2008), and activate RhoA (Haudenschild, D'Lima et al 2008). Cyclic dynamic compression can promote Smad2 phosphorylation (Bougault, Aubert-Foucher et al 2012), gene expression of MMP-13 (Nebelung, Gavenis et al 2012), which is the marker for catabolic changes in the ECM, and increases in ATP release (Garcia and Knight 2010). These studies demonstrate the sensitivity of chondrocytes to mechanical loading and indicate that a complete understanding chondrocyte mechanotransduction remains to be determined.…”

Section: Introductionmentioning

confidence: 99%

The mechanical microenvironment of high concentration agarose for applying deformation to primary chondrocytes

Zignego

Jutila

Gelbke

et al. 2014

Journal of Biomechanics

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Cartilage and chondrocytes experience loading that causes alterations in chondrocyte biological activity. In vivo chondrocytes are surrounded by a pericellular matrix with a stiffness of ∼25-200 kPa. Understanding the mechanical loading environment of the chondrocyte is of substantial interest for understanding chondrocyte mechanotransduction. The first objective of this study was to analyze the spatial variability of applied mechanical deformations in physiologically stiff agarose on cellular and sub-cellular length scales. Fluorescent microspheres were embedded in physiologically stiff agarose hydrogels. Microsphere positions were measured via confocal microscopy and used to calculate displacement and strain fields as a function of spatial position. The second objective was to assess the feasibility of encapsulating primary human chondrocytes in physiologically stiff agarose. The third objective was to determine if primary human chondrocytes could deform in high-stiffness agarose gels. Primary human chondrocyte viability was assessed using live-dead imaging following 24 and 72 hours in tissue culture. Chondrocyte shape was measured before and after application of 10% compression. These data indicate that (1) displacement and strain precision are ∼1% and 6.5% respectively, (2) high-stiffness agarose gels can maintain primary human chondrocyte viability of >95%, and (3) compression of chondrocytes in 4.5% agarose can induce shape changes indicative of cellular compression. Overall, these results demonstrate the feasibility of using high-concentration agarose for applying in vitro compression to chondrocytes as a model for understanding how chondrocytes respond to in vivo loading.

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Section: Introductionmentioning

confidence: 99%

The mechanical microenvironment of high concentration agarose for applying deformation to primary chondrocytes

Zignego

Jutila

Gelbke

et al. 2014

Journal of Biomechanics

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“…Another study using human chondrocytes were harvested from knee joints of patients having undergone total knee replacement and seeded into a collagen type I hydrogel, which were subjected to mechanical stimulation for 28 days with 10% continuous cyclic compressive loading at a frequency of 0.3 Hz. Then gene expression analyses revealed a significant increase in Agg and Col-2 under cyclical dynamic compressive loading 14) . These opposite results illustrated the difference of chondrocytes biosynthesis was attributed to the different scaffold materials, the different mechanical stimulation and the cell sources.…”

Section: Differences In Viscoelastic Properties Of Chondrocytes On DImentioning

confidence: 99%

Investigation for Effects of Cyclical Dynamic Compression on Matrix Metabolite and Mechanical Properties of Chondrocytes Cultured in Alginate

Zhou

Liu

Yang

et al. 2016

J. Hard Tissue Biology.

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Articular cartilage is suffered from high mechanical loads under normal physiological conditions and articular chondrocytes regulate the composition of peri-cellular matrix (PCM), in response to mechanical signals. This study aims to investigate influence of cyclical dynamic compression on matrix metabolite and mechanical properties of chondrocytes cultured in alginate. Two months old New Zealand white rabbits were sacrificed by air embolism. Chondrocytes were taken from knee joints under aseptic conditions and cultured in alginate. The suspension was gelled in a shape of disc in CaCl 2 solution and processed for intermittent compression by using Flexcell-5000 compression system kept under an uncompressed condition as a control. The gene regulation of aggrecan (Agg), collagen (Col-2), matrix metallo-proteinases 13 (MMP-13) and collagen X (Col-10) were determined by reverse transcription polymerase chain reaction (RT-PCR) at 7th, 14th and 21st day post loading. The alteration in mechanical properties of chondrocytes induced by compression was evaluated using micropipette aspiration technique combined with a half-space model. A significant up-regulation was observed in gene expression of Agg and Col-2 on 7th day or MMP-13 and Col-10 on 14th day respectively after loading of compression. In response to compression, chondrocytes exhibited viscoelastic solid creep behavior. Young's modulus almost approximated to control group (0.65±0.42kPa). However, viscoelastic properties decreased gradually along with intermittent compression. Viscoelastic properties in experimental 21st day, including equilibrium modulus (E ), the instantaneous modulus (E 0 ) and apparent viscosity (μ) were significantly lower than experimental 7th day and 14th day (P<0.001), no significant difference was found between experimental 7th day and 14th day (P >0.05). In conclusion, chondrocytes cultured in alginate are stable of mechanical properties and suitable to construct seed cell of tissue engineering, and can keep phenotype and mechanical properties.

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“…Furthermore, Ca 2 + oscillations have been shown to play significant roles in chondrogenesis, 17 chondrocyte matrix production, [18][19][20] and, potentially, the development of functional biomechanical properties in engineered cartilage. The complexity involved in using bioreactors to biomechanically stimulate engineered tissues, the potential confounding factors implicated in such processes, and the inconsistent results reported in the literature 8,21,22 have shifted interest to more direct methods. Much emphasis has instead been placed into the investigation of chemical agents that modulate known Ca 2 + -regulated molecular pathways as a means to improve the neotissue's functional properties.…”

Section: Introductionmentioning

confidence: 99%

“…In vitro experiments have shown that bioreactors that apply dynamic compression 8,9 and hydrostatic pressure 10,11 can induce chondrocytes to increase collagen and proteoglycan synthesis. Various mechanical stimuli, such as fluid flow-induced shear, 12 compression, [13][14][15] and hydrostatic pressure, 16 have also been shown to induce immediate increases in intracellular Ca 2 + .…”

Section: Introductionmentioning

confidence: 99%

Digoxin and Adenosine Triphosphate Enhance the Functional Properties of Tissue-Engineered Cartilage

Makris

Huang

et al. 2015

Tissue Engineering Part A

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Toward developing engineered cartilage for the treatment of cartilage defects, achieving relevant functional properties before implantation remains a significant challenge. Various chemical and mechanical stimuli have been used to enhance the functional properties of engineered musculoskeletal tissues. Recently, Ca 2 + -modulating agents have been used to enhance matrix synthesis and biomechanical properties of engineered cartilage. The objective of this study was to determine whether other known Ca 2 + modulators, digoxin and adenosine triphosphate (ATP), can be employed as novel stimuli to increase collagen synthesis and functional properties of engineered cartilage. Neocartilage constructs were formed by scaffold-free self-assembling of primary bovine articular chondrocytes. Digoxin, ATP, or both agents were added to the culture medium for 1 h/ day on days 10-14. After 4 weeks of culture, neocartilage properties were assessed for gross morphology, biochemical composition, and biomechanical properties. Digoxin and ATP were found to increase neocartilage collagen content by 52-110% over untreated controls, while maintaining proteoglycan content near native tissue values. Furthermore, digoxin and ATP increased the tensile modulus by 280% and 180%, respectively, while the application of both agents increased the modulus by 380%. The trends in tensile properties were found to correlate with the amount of collagen cross-linking. Live Ca 2 + imaging experiments revealed that both digoxin and ATP were able to increase Ca 2 + oscillations in monolayer-cultured chondrocytes. This study provides a novel approach toward directing neocartilage maturation and enhancing its functional properties using novel Ca 2 + modulators.

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Simultaneous anabolic and catabolic responses of human chondrocytes seeded in collagen hydrogels to long-term continuous dynamic compression

Cited by 35 publications

References 42 publications

The mechanical microenvironment of high concentration agarose for applying deformation to primary chondrocytes

The mechanical microenvironment of high concentration agarose for applying deformation to primary chondrocytes

Investigation for Effects of Cyclical Dynamic Compression on Matrix Metabolite and Mechanical Properties of Chondrocytes Cultured in Alginate

Digoxin and Adenosine Triphosphate Enhance the Functional Properties of Tissue-Engineered Cartilage

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