Open Access

Mario Rothbauer, Ruth A. Byrne, Silvia Schobesberger, Isabel Olmos Calvo, Anita Fischer, Eva I. Reihs, Sarah Spitz, Barbara Bachmann, Florian Sevelda, Johannes Holinka, Wolfgang Holnthoner, Heinz Redl, Stefan Toegel, Reinhard Windhager, Hans P. Kiener, Peter Ertl

• Rheumatoid arthritis is characterised by a progressive, intermittent inflammation at the synovial membrane, which ultimately leads to the destruction of the synovial joint. The synovial membrane as the joint capsule's inner layer is lined with fibroblast-like synoviocytes that are the key player supporting persistent arthritis leading to bone erosion and cartilage destruction. While microfluidic models that model molecular aspects of bone erosion between bone-derived cells and synoviocytes have been established, RA's synovial-chondral axis has not yet been realised using a microfluidic 3D model based on human patient in vitro cultures. Consequently, we established a chip-based three-dimensional tissue coculture model that simulates the reciprocal cross talk between individual synovial and chondral organoids. When co-cultivated with synovial organoids, we could demonstrate that chondral organoids induce a higher degree of cartilage physiology and architecture and show differential cytokine response compared to their respective monocultures highlighting the importance of reciprocal tissue-level cross talk in the modelling of arthritic diseases.