Joint-on-a-Chip: : A rheumatoid arthritis disease model for drug screening

Abstract

Rheumatoid arthritis is an autoimmune disease and causes inflamed joints through recruitment of immune cells, synovitis as well as degradation of cartilage. Patients suffer from joint pain, are limited in their daily activities and have a lower life expectancy. Almost 1% of the population worldwide are affected and live without perspective of a real cure. Indeed, drugs are available to reduce pain and decrease disease progression, however remission is achieved in less than 50% of patients. In addition, there is a long in-patient trial period since individual’s respond differently to the drugs or show different disease patterns. Therefore, alternative methods for fast and effective drug screening are an urgent need. The emerging technology of organ-on-a-chip could provide a chip platform as an alternative to animal models to study new drug targets. Furthermore, it is applicable for personalized medicine as a fast drug screening platform to find the suitable drugs for each individual patient. This study aimed to develop a joint-on-a-chip to mimic the physiological environment of a human diarthrodial joint and provide a 3D model to investigate joint diseases such as rheumatoid arthritis. The designed chip was characterized by analyzing the behavior of the cells and offered reproducible 3D cell cultures through features such as a “hydrogel stopper” and “hydrogel condensation guide”. Patients derived synovial cells were analyzed and a high patient variability could be observed. The presence of immune cells in early passages could be related to increased inflammatory marker IL-6 secretion. Leucocyte presence limited the ability of micromass formation regarding their lining/sublining architecture. In addition, a protocol for a co-culture of synovial fibroblast and chondrocytes was established. Through further validation of this implemented system, the developed chip could provide a reliable human 3D model of rheumatoid arthritis, but also of other joint diseases such as osteoarthritis.