Abstract

Joint on Chip Technology: A New Era in Studying Rheumatic Disorders

Marcel Karperien, Professor, Developmental BioEngineering, MIRA Institute for Biomedical Technology & Technical Medicine, University of Twente

Degenerative joint diseases such as osteoarthritis are a major and rising health care problem which cannot be effectively treated. Consequently there is a large unmet need for disease modifying treatments, with many attempts failed at phase 2 and 3 clinical trials due to lack of efficacy in recent years. This is in part due to the lack of translational power of frequently used animal models. To address this issue we have engineered the first prototypes of a cartilage-on-chip and a synovial membrane-on-chip which can be combined in a multi-organ on-chip device; the Joint-on-Chip (JoC) and have started the engineering of Hoffa’s fat pad- and ligament-on-chip. Our work on the cartilage-on-chip and the synovial membrane-on-chip is most advanced. Each of these chip models is complemented with mechanical actuation units enabling the controlled loading of the tissue. Loading regimes mimic the rolling motion of the moving joint. Indeed in our cartilage-on-chip model we showed that emulating the rolling motion of the joint resulted in the deposition of more cartilaginous matrix composed of glycosaminoglycans and collagen 2 and 6. It also induced the formation of a pericellular matrix. Matrix formation was much more abundant than in the devices exposed to compression only and to static culture in which there was virtually no matrix formation. This suggests that a combination of compression and shear stress such as uniquely seen during a rolling motion is beneficial for cartilage formation. In the synovial membrane-on-chip we were able to emulate the intima consisting of a cell layer of synoviocytes and macrophages. Challenging this intima with proinflammatory cytokines evoked a classical inflammatory response with increased mRNA expression of matrix degrading enzymes and pro-inflammatory cytokines and chemokines and upregulation of markers typically present in rheumatoid arthritis. In my presentation I will show a few examples how we are using these devices in drug screening to identify dearly needed new disease modifying treatments for degenerative joint diseases. In conclusion, we have successfully engineered models emulating key tissues of the articulating joint which will allow us to develop disease models for rheumatic diseases. In my presentation I will show a few examples how we are using these devices in drug screening to identify dearly needed new disease modifying treatments for degenerative joint diseases.