Using Microphysiological System for the Development of Treatments for Joint Inflammation and Associated Cartilage Loss-A Pilot Study.

Abstract

Osteoarthritis (OA) is a painful and disabling joint disease affecting millions worldwide. The lack of clinically relevant models limits our ability to predict therapeutic outcomes prior to clinical trials, where most drugs fail. Therefore, there is a need for a model that accurately recapitulates the whole-joint disease nature of OA in humans. Emerging microphysiological systems provide a new opportunity. We recently established a miniature knee joint system, known as the miniJoint, in which human bone-marrow-derived mesenchymal stem cells (hBMSCs) were used to create an osteochondral complex, synovial-like fibrous tissue, and adipose tissue analogs. In this study, we explored the potential of the miniJoint in developing novel treatments for OA by testing the hypothesis that co-treatment with anti-inflammation and chondroinducing agents can suppress joint inflammation and associated cartilage degradation. Specifically, we created a "synovitis"-relevant OA model in the miniJoint by treating synovial-like tissues with interleukin-1β (IL-1β), and then a combined treatment of oligodeoxynucleotides (ODNs) suppressing the nuclear factor kappa beta (NF-κB) genetic pathway and bone morphogenic protein-7 (BMP-7) was introduced. The combined treatment with BMP-7 and ODNs reduced inflammation in the synovial-like fibrous tissue and showed an increase in glycosaminoglycan formation in the cartilage portion of the osteochondral complex. For the first time, this study demonstrated the potential of the miniJoint in developing disease-modifying OA drugs. The therapeutic efficacy of co-treatment with NF-κB ODNs and BMP-7 can be further validated in future clinical studies.