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Development of a Microfluidic Vascularized Osteochondral Model as a Drug Testing Platform for Osteoarthritis
Shima Salehi1, Stefania Brambilla1, Marco Rasponi2
1Cell and Tissue Engineering Laboratory, IRCCS Istituto Ortopedico Galeazzi, Via Belgioioso 173, Milan, 20157, Italy.
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-1β 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.
Insights
A new microfluidic model using human cells mimics osteoarthritis (OA) to test drugs. This advanced model, including cartilage and bone, shows promise for developing effective OA treatments.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a degenerative joint disease with no current drugs to halt its progression.
- Existing models lack the cellular complexity to accurately represent OA's pathophysiology.
- Developing effective OA treatments is hindered by inadequate preclinical models.
Purpose of the Study:
- To develop and validate an osteochondral microfluidic model using human primary cells.
- To mimic an osteoarthritis-like microenvironment for drug testing.
- To assess the necessity of incorporating both cartilage and bone compartments for OA modeling.
Main Methods:
- Constructed a microfluidic device with separate cartilage (chondrocytes in fibrin hydrogel) and bone (osteoblasts, osteoclasts, endothelial cells, MSCs in fibrin hydrogel with nanoparticles) compartments.
- Induced OA-like conditions using Interleukin-1β.
- Evaluated drug efficacy using anti-inflammatory drugs (Interleukin-1 Receptor antagonist, Celecoxib) by measuring inflammation and matrix degradation markers.
Main Results:
- The model successfully mimicked OA-like conditions and inflammation.
- The model demonstrated differential drug efficacy, validating its potential as a drug testing platform.
- Comparison revealed that the 'Cartilage+Bone' model better captured OA pathophysiology than the 'Cartilage' model alone.
Conclusions:
- The developed osteochondral microfluidic model is a valuable platform for osteoarthritis drug discovery.
- Incorporating both cartilage and bone components is crucial for accurately recapitulating OA.
- This model offers a more biologically relevant system for testing therapeutic interventions for osteoarthritis.
