Cartilage-On-Chip Platform For Drug Screening In Osteoarthritis

Purpose: Osteoarthritis (OA) is a complex disease in which many factors play a role. Developing a disease-modifying treatment is therefore challenging and has not resulted in clinically available therapeutics yet. Potential therapeutics have often shown success in vitro and in animal models, but they fail in clinical trials. This is mainly due to the fact that currently used disease models, both in vitro and animal models, have several disadvantages and do not accurately mimic the complexity of human disease. A humanized organ-on-chip platform could close this gap in order to improve drug screening. This platform has been developed previously in our group as a cartilage-on-chip device, in which human chondrocytes are cultured in an agarose hydrogel and can be mechanically loaded by a pressurized air chamber. In this way, loading of the cartilage layer during movement could be mimicked on chip. For simulating the cartilage in OA it is important that also the inflammatory character of OA is incorporated in this platform, for example by stimulating chondrocytes with pro-inflammatory cytokines such as IL-1b to mimic an OA-like environment. Presently, not much is known about the interaction between IL-1b and biomechanical stimulation of chondrocytes. The aim of this study was to evaluate the effect of cytokine stimulation and mechanical loading on chondrocytes in a cartilage on chip platform. The expression and activity of matrix metalloproteinase 9 (MMP9) and the expression of collagen I and II were used as a read-out.