An integrated cartilage-on-a-chip recapitulating the bio-chemo-mechanical microenvironment in osteoarthritic joints

Osteoarthritis (OA), the most common chronic joint disease, leads to remarkable morbidity and disability. The development of preclinical models that accurately recapitulate the bio-chemo-mechanical microenvironment of osteoarthritic joints is crucial for elucidating OA pathogenesis and facilitating drug development. In this study, we present a microfluidics-based cartilage-on-a-chip model that integrates tunable mechanical stimulation and inter-tissue/cell communication, mimicking the key physiological characteristics of articular cartilage for organ-level OA research. By applying controllable mechanical compression, we established a model that captures healthy and injury hallmarks of the cartilage and directly observed the mechanotransduction responses in chondrocytes. We further demonstrated that mechanically damaged cartilage induces synovial abnormalities and immune dysregulation and explored the potential of our chip as a platform for screening therapeutic targets. This cartilage-on-a-chip offers an in vitro system with a close-to-in vivo microenvironment for investigating complex bio-chemo-mechanical interactions, paving the way for advanced studies on OA pathogenesis and drug screening. (Figure presented.)