A personalized osteoarthritic joint-on-a-chip as a screening platform for biological treatments

Abstract

Osteoarthritis (OA) is a highly disabling pathology, characterized by synovial inflammation and cartilage degeneration. Orthobiologics have shown promising results in OA treatment thanks to their ability to influence articular cells and modulate the inflammatory OA environment. Considering their complex mechanism of action, the development of reliable and relevant joint models appears as crucial to select the best orthobiologics for each patient.The aim of this study was to establish a microfluidic OA model to test therapies in a personalized human setting. The joint-on-a-chip model included cartilage and synovial compartments, containing hydrogel-embedded chondrocytes and synovial fibroblasts, separated by a channel for synovial fluid. For the cartilage compartment, a Hyaluronic Acid-based matrix was selected to preserve chondrocyte phenotype. Adding OA synovial fluid induced the production of inflammatory cytokines and degradative enzymes, generating an OA microenvironment. Personalized models were generated using patient-matched cells and synovial fluid to test the efficacy of mesenchymal stem cells on OA signatures. The patient-specific models allowed monitoring changes induced by cell injection, highlighting different individual responses to the treatment. Altogether, these results support the use of this joint-on-a-chip model as a prognostic tool to screen the patient-specific efficacy of orthobiologics.