Development of a Microfluidic Vascularized Osteochondral Model as a Drug Testing Platform for Osteoarthritis.

ABSTRACT

Osteoarthritis (OA) is a degenerative joint disease characterized by changes in cartilage and subchondral bone. To date, there are no available drugs that can counteract the progression of OA, partly due to the inadequacy of current models to recapitulate the relevant cellular complexity. In this study, an osteochondral microfluidic model is developed using human primary cells to mimic an OA-like microenvironment and this study validates it as a drug testing platform. In the model, the cartilage compartment is created by embedding articular chondrocytes in fibrin hydrogel while the bone compartment is obtained by embedding osteoblasts, osteoclasts, endothelial cells, and mesenchymal stem cells in a fibrin hydrogel enriched with calcium phosphate nanoparticles. After developing and characterizing the model, Interleukin-1ß is applied to induce OA-like conditions. Subsequently, the model potential is evaluated as a drug testing platform by assessing the effect of two anti-inflammatory drugs (Interleukin-1 Receptor antagonist and Celecoxib) on the regulation of inflammation- and matrix degradation-related markers. The model responded to inflammation and demonstrated differences in drug efficacy. Finally, it compares the behavior of the "Cartilage" and "Cartilage+Bone" models, emphasizing the necessity of incorporating both cartilage and bone compartments to capture the complex pathophysiology of OA.