Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip model

Occhetta, Paola; Mainardi, Andrea; Votta, Emiliano; Vallmajó-Martín, Queralt; Ehrbar, Martin; Martín, Iván; Barbero, Andrea; Rasponi, Marco

doi:10.1038/s41551-019-0406-3

Cited by 136 publications

(148 citation statements)

References 69 publications

Supporting

Mentioning

142

Contrasting

Order By: Relevance

“…Finally, our results demonstrated that fluid dynamic stimulation plays a very important role also after spheroid formation influencing GAG deposition. These results are not unexpected, since in several studies, biophysical cues have been applied to stimulate 3D constructs through micro-and macro-scale systems, demonstrating their effects on chondrocyte phenotype (Raimondi et al, 2011;Mayer et al, 2016;Salinas et al, 2018;Occhetta et al, 2019;Sharifi and Gharravi, 2019). Alcian blue staining showed that, regardless of the flow rate, the pellet region in direct contact with culture medium was characterized by a higher amount of GAGs.…”

Section: Discussionsupporting

confidence: 54%

Microfluidic Biofabrication of 3D Multicellular Spheroids by Modulation of Non-geometrical Parameters

Lopa

Piraino

Talò

et al. 2020

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

Three-dimensional (3D) cell spheroids are being increasingly applied in many research fields due to their enhanced biological functions as compared to conventional twodimensional (2D) cultures. 3D cell spheroids can replicate tissue functions, which enables their use both as in vitro models and as building blocks in tissue biofabrication approaches. In this study, we developed a perfusable microfluidic platform suitable for robust and reproducible 3D cell spheroid formation and tissue maturation. The geometry of the device was optimized through computational fluid dynamic (CFD) simulations to improve cell trapping. Experimental data were used in turn to generate a model able to predict the number of trapped cells as a function of cell concentration, flow rate, and seeding time. We demonstrated that tuning non-geometrical parameters it is possible to control the size and shape of 3D cell spheroids generated using articular chondrocytes (ACs) as cellular model. After seeding, cells were cultured under perfusion at different flow rates (20, 100, and 500 µl/min), which induced the formation of conical and spherical spheroids. Wall shear stress values on cell spheroids, computed by CFD simulations, increased accordingly to the flow rate while remaining under the chondroprotective threshold in all configurations. The effect of flow rate on cell number, metabolic activity, and tissue-specific matrix deposition was evaluated and correlated with fluid velocity and shear stress distribution. The obtained results demonstrated that our device represents a helpful tool to generate stable 3D cell spheroids which can find application both to develop advanced in vitro models for the study of physiopathological tissue maturation mechanisms and to obtain building blocks for the biofabrication of macrotissues.

show abstract

Section: Discussionsupporting

confidence: 54%

Microfluidic Biofabrication of 3D Multicellular Spheroids by Modulation of Non-geometrical Parameters

Lopa

Piraino

Talò

et al. 2020

Front. Bioeng. Biotechnol.

Self Cite

View full text Add to dashboard Cite

show abstract

“…As with the native ECM, the physical and biological properties of hydrogels can be tuned to regulate cellular behaviours. Hydrogels have thus been widely exploited to direct stem cell differentiation and tissue formation 1 , and as material systems to create tissue and tissue models of disease 2,3 .…”

Section: Ulrich Blache Molly M Stevens and Eileen Gentlemanmentioning

confidence: 99%

Harnessing the secreted extracellular matrix to engineer tissues

2020

View full text Add to dashboard Cite

show abstract

“…For example, to model excessive mechanical loading-induced OA chondrocyte phenotypes, Occhetta et al [ 249 ] used human articular chondrocyte-laden hydrogels to develop a 3D human cartilage-on-a-chip (COC) constructed on polydimethylsiloxane (PDMS) ( Figure 3 A,B). Under hyperphysiological confined compression (30% confined compression; Figure 3 C), the cartilage microtissues in this microfluidic device displayed increased expression of catabolic enzymes and inflammatory markers, and chondrocyte hypertrophy [ 249 ]. Another PDMS-based COC device was designed as an in vitro model of equine OA [ 250 ].…”

Section: Experimental Modelsmentioning

confidence: 99%

Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models

Alexander

et al. 2020

Biology

134

View full text Add to dashboard Cite

As the most common chronic degenerative joint disease, osteoarthritis (OA) is the leading cause of pain and physical disability, affecting millions of people worldwide. Mainly characterized by articular cartilage degradation, osteophyte formation, subchondral bone remodeling, and synovial inflammation, OA is a heterogeneous disease that impacts all component tissues of the articular joint organ. Pathological changes, and thus symptoms, vary from person to person, underscoring the critical need of personalized therapies. However, there has only been limited progress towards the prevention and treatment of OA, and there are no approved effective disease-modifying osteoarthritis drugs (DMOADs). Conventional treatments, including non-steroidal anti-inflammatory drugs (NSAIDs) and physical therapy, are still the major remedies to manage the symptoms until the need for total joint replacement. In this review, we provide an update of the known OA risk factors and relevant mechanisms of action. In addition, given that the lack of biologically relevant models to recapitulate human OA pathogenesis represents one of the major roadblocks in developing DMOADs, we discuss current in vivo and in vitro experimental OA models, with special emphasis on recent development and application potential of human cell-derived microphysiological tissue chip platforms.

show abstract

Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip model

Cited by 136 publications

References 69 publications

Microfluidic Biofabrication of 3D Multicellular Spheroids by Modulation of Non-geometrical Parameters

Microfluidic Biofabrication of 3D Multicellular Spheroids by Modulation of Non-geometrical Parameters

Harnessing the secreted extracellular matrix to engineer tissues

Pathogenesis of Osteoarthritis: Risk Factors, Regulatory Pathways in Chondrocytes, and Experimental Models

Contact Info

Product

Resources

About