Owing to population aging, the social impact of osteoarthritis (OA)—the most common musculoskeletal disease—is expected to increase dramatically. Yet, therapy is still limited to palliative treatments or surgical intervention, and disease-modifying OA (DMOA) drugs are scarce, mainly because of the absence of relevant preclinical OA models. Therefore, in vitro models that can reliably predict the efficacy of DMOA drugs are needed. Here, we show, using a newly developed microphysiological cartilage-on-a-chip model that enables the application of strain-controlled compression to three-dimensional articular cartilage microtissue, that a 30% confined compression recapitulates the mechanical factors involved in OA pathogenesis and is sufficient to induce OA traits. Such hyperphysiological compression triggers a shift in cartilage homeostasis towards catabolism and inflammation, hypertrophy, and the acquisition of a gene expression profile akin to those seen in clinical osteoarthritic tissue. The cartilage on-a-chip model may enable the screening of DMOA candidates.
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Modeling early changes associated with cartilage trauma using human-cell-laden hydrogel cartilage models
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The main data supporting the findings of this study are available within the paper and its Supplementary Information. All data generated for this study are available from the corresponding author upon reasonable request.
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We are grateful to G. Pagenstert for provision of the articular cartilage biopsies. We also thank Fidia Farmaceutici (Italy) for provision of the HYADD 4 and LMW-HA compounds—in particular, D. Galesso, R. Beninatto and C. Guarise for feedback on the results. Device manufacturing was partially performed at PoliFAB—the micro- and nanofabrication facility of Politecnico di Milano. This work was partially funded by the Swiss National Science Foundation (numbers 310030_149614/1 and 310030_175660/1).
The authors declare no competing interests.
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Occhetta, P., Mainardi, A., Votta, E. et al. Hyperphysiological compression of articular cartilage induces an osteoarthritic phenotype in a cartilage-on-a-chip model. Nat Biomed Eng 3, 545–557 (2019). https://doi.org/10.1038/s41551-019-0406-3
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