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Updated: Jun 26, 2025

Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs
Published on: January 27, 2023
A personalized osteoarthritic joint-on-a-chip as a screening platform for biological treatments
Dalila Petta1,2, Daniele D'Arrigo1,2,3, Shima Salehi4
1Regenerative Medicine Technologies Lab, Laboratories for Translational Research, Ente Ospedaliero Cantonale, Via Chiesa, 5, 6500, Bellinzona, Switzerland.
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.
Insights
A novel joint-on-a-chip model replicates osteoarthritis (OA) in a personalized human setting. This microfluidic system effectively tests orthobiologic therapies, like mesenchymal stem cells, predicting patient-specific treatment responses for osteoarthritis.
Area of Science:
- Biotechnology
- Regenerative Medicine
- Biomaterials Science
Background:
- Osteoarthritis (OA) is a debilitating joint disease marked by inflammation and cartilage breakdown.
- Orthobiologics offer potential OA treatments by modulating the joint environment and cells.
- Developing accurate models is vital for selecting personalized orthobiologic therapies.
Purpose of the Study:
- To create a microfluidic joint-on-a-chip model for personalized osteoarthritis therapy testing.
- To establish a platform for evaluating orthobiologics in a patient-specific human context.
Main Methods:
- A microfluidic joint model with separate cartilage and synovial compartments was engineered.
- Hydrogel-embedded chondrocytes and synovial fibroblasts were utilized, with a channel for synovial fluid.
- Patient-derived cells and synovial fluid were used to create personalized OA microenvironments.
- Mesenchymal stem cells were tested for efficacy on OA biomarkers within these personalized models.
Main Results:
- The model successfully simulated an OA microenvironment by incorporating OA synovial fluid, inducing inflammatory cytokines and degradative enzymes.
- Personalized models demonstrated varying patient responses to mesenchymal stem cell therapy.
- The joint-on-a-chip system allowed for monitoring treatment-induced changes and individual therapeutic efficacy.
Conclusions:
- The developed joint-on-a-chip model serves as a valuable prognostic tool for screening patient-specific orthobiologic efficacy.
- This platform facilitates personalized medicine approaches in osteoarthritis treatment.
- The model aids in understanding individual responses to regenerative therapies for osteoarthritis.

