Recapitulating monocyte extravasation to the synovium in an organotypic microfluidic model of the articular joint

Abstract The synovium of osteoarthritis (OA) patients can be characterized by an abnormal accumulation macrophages originating from extravasated monocytes. Since targeting monocyte extravasation may represent a promising therapeutic strategy, our aim was to develop organotypic microfluidic model recapitulating this process. Synovium and cartilage were modeled hydrogel-embedded OA synovial fibroblasts articular chondrocytes separated fluid channel. compartment included perfusable endothelialized channel dedicated injection. Monocyte in response chemokines quantified. efficacy chemokine receptor antagonists, RS-504393 (CCR2 antagonist) Cenicriviroc (CCR2/CCR5 inhibiting tested pre-incubating monocytes with the antagonists before After designing fabricating chip, culture conditions optimized achieve including fibroblasts, chondrocytes, continuous endothelial monolayer expressing intercellular adhesion molecule-1 vascular cell molecule-1. A significantly higher number mix ( p < 0.01) 0.01), compared control condition. In both cases, endothelium pre-activation enhanced extravasation. simultaneous blocking CCR2 CCR5 proved more effective 0.001) than only 0.01). study provided direct evidence that induces cross invade compartment. exploited either test molecules antagonizing process or investigate effect on cells.