A vascularized microfluidic model of the osteochondral unit for modeling inflammatory response and therapeutic screening

Abstract

Osteoarthritis (OA) has long been considered a disease of the articular cartilage. Within the past decade it has become increasingly clear that OA is a disease of the entire joint space and that interactions between articular cartilage and subchondral bone likely play an important role in the disease. Driven by this knowledge, we have created a novel microphysiological model of the osteochondral unit containing synovium, cartilage, bone, and vasculature in separate compartments with molecular and direct cell–cell interaction between the cells from the different tissue types. We have characterized the model in terms of differentiation by molecule and matrix secretion and shown that it demonstrates morphology and functionality that mimic the native characteristic of the joint space. Finally, we induced inflammation and subsequently rescued the model constructs by a known compound as proof of concept for anti-inflammatory drug screening applications.