Development of a Synovium-on-a-Chip Microphysiological System to Interrogate Pathobiology and Enhance Precision Medicine in Rheumatoid Arthritis

PROJECT SUMMARY Rheumatoid arthritis (RA) is the most common inflammatory joint disease caused by a chronic inflammation in joints, where no effective treatment is currently available. Currently there is no effective model can accurately dissect RA pathogenesis and consistently predict the effect of a therapeutic agent in patients. Better model systems that can accurately recapitulate the immune responses and pathological processes of RA in the human synovial microenvironment with immunomodulatory treatments are critically required. In this work we aim to develop a fully patient-derived in vitro RA disease model termed “Synovium-on-a-Chip” by including full spectrum of synovial cell types, which can serve as a precision medicine platform to (1) interrogate human RA pathobiology and to (2) achieve "clinical trial on chips" for stratifying patients and pre-screening of novel immunotherapy. Simulating the structure and inflammatory microenvironment of the synovium with such a biomimetic vascularized immunocompetent microphysiological system will represent a major advance over existing models, providing much greater biomimicry and enabling next-step studies to allow rational selection of immunomodulatory drugs to personalize treatment of RA patients.