Developing a joint-on-chip platform: A multi-organ-on-chip model to mimic healthy and diseased conditions of the synovial joints

Arthritis affects millions of people worldwide. With only a few disease-modifying drugs available for treatment of rheumatoid arthritis and none for osteoarthritis, a clear need exists for new treatment options. Current disease models used for drug screening and development suffer from several disadvantages and most importantly, do not accurately emulate all facets of human joint diseases. A humanized joint-on-chip (JoC) model or platform could revolutionize research and drug development in rheumatic diseases. A JoC model is a multi-organ-on-chip platform that incorporates a range of engineered features to emulate essential aspects and functions of the human joint and faithfully recapitulates the joint’s physiological responses. In this thesis we propose an architecture of such JoC platform. Furthermore, we present a cartilage-on-chip and a synovial membrane-on-chip models which function as a minimal functional unit for drug screening and biomarker investigation. The first model incorporates a mechanical actuation unit to emulate the forces exerted onto the cartilage during movement and shows promising results in terms of matrix maturation and cell differentiation. The synovial membrane model incorporates the immune system, an essential component in disease development. Here, by adding inflammatory cytokines it is possible to trigger an inflammation similar to arthritic diseases. The end goal is to obtain a reliable and ready-to-use humanized model of the joint for studying the pathophysiology of rheumatic diseases and screening drugs for treatment of these conditions.