02486nas a2200385   4500000000100000008004100001260001200042653001400054653002400068653001700092653002000109653002700129653001800156653001900174653001900193100001700212700002100229700001700250700001900267700002000286700001700306700001700323700001900340700002000359700002300379700001900402700001600421700002000437245010000457856007200557300001100629490000700640520143900647022001402086       2024                            d  c2024-0610aCartilage10aChondrogenic matrix10aInflammation10aJoint-on-a-chip10aMesenchymal stem cells10amicrofluidics10aOrthobiologics10aOsteoarthritis1 aDalila Petta1 aDaniele D'Arrigo1 aShima Salehi1 aGiuseppe Talò1 aLorenzo Bonetti1 aMarco Vanoni1 aLuca Deabate1 aLuigi De Nardo1 aGabriele Dubini1 aChristian Candrian1 aMatteo Moretti1 aSilvia Lopa1 aChiara Arrigoni00aA personalized osteoarthritic joint-on-a-chip as a screening platform for biological treatments  uhttps://www.sciencedirect.com/science/article/pii/S2590006424001315  a1010720 v263 aOsteoarthritis (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.  a2590-0064