Related Experiment Video
Updated: Aug 9, 2025
Creation of a Knee Joint-on-a-Chip for Modeling Joint Diseases and Testing Drugs
Published on: January 27, 2023
Using Microphysiological System for the Development of Treatments for Joint Inflammation and Associated Cartilage
Meagan J Makarczyk1,2, Sophie Hines1, Haruyo Yagi1
1Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 450 Technology Drive, Rm 217, Pittsburgh, PA 15219, USA.
Abstract:
Osteoarthritis (OA) is a painful and disabling joint disease affecting millions worldwide. The lack of clinically relevant models limits our ability to predict therapeutic outcomes prior to clinical trials, where most drugs fail. Therefore, there is a need for a model that accurately recapitulates the whole-joint disease nature of OA in humans. Emerging microphysiological systems provide a new opportunity. We recently established a miniature knee joint system, known as the miniJoint, in which human bone-marrow-derived mesenchymal stem cells (hBMSCs) were used to create an osteochondral complex, synovial-like fibrous tissue, and adipose tissue analogs. In this study, we explored the potential of the miniJoint in developing novel treatments for OA by testing the hypothesis that co-treatment with anti-inflammation and chondroinducing agents can suppress joint inflammation and associated cartilage degradation. Specifically, we created a "synovitis"-relevant OA model in the miniJoint by treating synovial-like tissues with interleukin-1β (IL-1β), and then a combined treatment of oligodeoxynucleotides (ODNs) suppressing the nuclear factor kappa beta (NF-κB) genetic pathway and bone morphogenic protein-7 (BMP-7) was introduced. The combined treatment with BMP-7 and ODNs reduced inflammation in the synovial-like fibrous tissue and showed an increase in glycosaminoglycan formation in the cartilage portion of the osteochondral complex. For the first time, this study demonstrated the potential of the miniJoint in developing disease-modifying OA drugs. The therapeutic efficacy of co-treatment with NF-κB ODNs and BMP-7 can be further validated in future clinical studies.
Insights
A novel miniature knee joint model (miniJoint) successfully simulated osteoarthritis (OA) and demonstrated that combined anti-inflammatory and cartilage-regenerating treatments can reduce joint inflammation and cartilage damage in OA models.
Area of Science:
- Biomedical Engineering
- Regenerative Medicine
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a prevalent, debilitating joint disease impacting millions globally.
- Current preclinical models often fail to accurately predict therapeutic outcomes in clinical trials.
- There is a critical need for advanced models that replicate the complex, whole-joint nature of human OA.
Purpose of the Study:
- To evaluate the potential of a novel miniature knee joint system (miniJoint) for developing new OA treatments.
- To test the hypothesis that combined anti-inflammatory and chondro-inductive agents can mitigate OA-related joint inflammation and cartilage degradation.
- To establish a synovitis-relevant OA model within the miniJoint system.
Main Methods:
- Developed a miniJoint system using human bone-marrow-derived mesenchymal stem cells (hBMSCs) to create osteochondral, synovial-like, and adipose tissue analogs.
- Induced a synovitis-associated OA model by treating synovial-like tissues with interleukin-1β (IL-1β).
- Administered a combination therapy of nuclear factor kappa beta (NF-κB) pathway-suppressing oligodeoxynucleotides (ODNs) and bone morphogenic protein-7 (BMP-7).
Main Results:
- The combined BMP-7 and ODN treatment effectively reduced inflammation in the synovial-like fibrous tissue.
- Significant increases in glycosaminoglycan formation were observed in the cartilage portion of the osteochondral complex.
- The miniJoint system successfully modeled OA-related inflammation and cartilage changes.
Conclusions:
- The miniJoint system holds significant potential for the preclinical development of disease-modifying OA drugs.
- The co-treatment with NF-κB ODNs and BMP-7 demonstrated therapeutic efficacy in suppressing inflammation and promoting cartilage health.
- Further validation of this therapeutic approach is warranted in future clinical studies.
