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Stem cell-based microphysiological osteochondral system to model tissue response to interleukin-1β.
Hang Lin1, Thomas P Lozito, Peter G Alexander
1Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine , Pittsburgh, Pennsylvania 15219, United States.
Molecular Pharmaceutics
|May 17, 2014
Summary
This study developed a novel microfluidic bioreactor to engineer osteochondral tissue, revealing communication between bone and cartilage that influences osteoarthritis progression and drug testing.
Area of Science:
- Biomaterials Engineering
- Tissue Engineering
- Osteoarthritis Research
Background:
- Osteoarthritis (OA) is a degenerative joint disease affecting bone and cartilage.
- Understanding OA pathogenesis and developing disease-modifying drugs (DMOADs) requires physiological models.
- Current models lack the complexity to replicate osteochondral interactions.
Purpose of the Study:
- To engineer functional osteochondral tissue in vitro.
- To investigate the pathogenic mechanisms of OA using a novel bioreactor system.
- To establish a platform for testing potential DMOADs.
Main Methods:
- Fabrication of a multichamber microfluidic bioreactor.
- In situ fabrication and culture of human bone marrow stem cell (hBMSC)-derived osteochondral constructs.
- Induction of chondrogenic and osteogenic differentiation with tissue-specific media.
- Application of interleukin-1β (IL-1β) to assess degradative responses.
Main Results:
- Successful engineering of osteochondral tissue with distinct chondral and osseous layers.
- Observed tissue-specific gene expression, matrix production, and a tidemark interface.
- IL-1β induced significant degradative responses in both local and opposing tissues.
- Osseous IL-1β application caused greater chondral degradation, indicating cross-talk.
Conclusions:
- The developed microtissue culture system effectively mimics osteochondral tissue physiology.
- Demonstrated active biochemical communication between bone and cartilage layers in OA.
- The system serves as a valuable platform for OA research and DMOAD screening.
