AccScience Publishing / OR / Volume 1 / Issue 1 / DOI: 10.36922/or.8461
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ORIGINAL RESEARCH ARTICLE

Cartilage-on-chip for osteoarthritis drug screening

Jing Zhao1,2,3† ,  Fuming Shen1,2,3† ,  Shihao Sheng4† ,  Jian Wang1,2,3 ,  Miaomiao Wang1,2 ,  Fuxiao Wang1,2 ,  Yingying Jiang1,2 ,  Yingying Jing1,2 ,  Ke Xu1,2,5,6,7* ,  Jiacan Su1,2,4,5,6,7*
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1 Institute of Translational Medicine, Shanghai University, Shanghai, Shanghai, China
2 Organoid Research Center, Shanghai University, Shanghai, Shanghai, China
3 School of Medicine, Shanghai University, Shanghai, Shanghai, China
4 Department of Orthopedics, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, Shanghai, China
5 Wenzhou Institute of Shanghai University, Shanghai University, Wenzhou, Zhejiang, China
6 Sanming Institute of Translational Medicine, Sanming, Fujian, China
7 Wenzhou Key Laboratory of Tissue Regeneration Medical Materials, Wenzhou, China
†These authors contributed equally to this work.
OR 2025, 1(1), 8461 https://doi.org/10.36922/or.8461
Submitted: 8 January 2025 | Revised: 3 March 2025 | Accepted: 7 March 2025 | Published: 25 March 2025
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution -Noncommercial 4.0 International License (CC-by the license) ( https://creativecommons.org/licenses/by-nc/4.0/ )
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Abstract

Osteoarthritis (OA) is a common disease characterized by degenerative changes in joint cartilage, manifesting clinically as joint pain, stiffness, and functional impairment. At present, the variety of drugs available for OA is relatively limited, and these primarily serve to alleviate symptoms rather than effectuate actual cartilage repair. The complex cellular environment and biochemical reactions within cartilage tissue further complicate the screening of effective drugs. Organ-on-a-chip is increasingly being applied in the field of drug screening with its ability to mimic the microenvironment and physiological functions of human organs. Herein, we developed a cartilage-on-chip by culturing primary chondrocytes in three dimensions within a microfluidic system. This novel design could maintain the cartilage phenotype and replicate its microenvironment. This cartilage-on-chip cultured under interleukin-1 beta for 3 days displayed a distinct OA-like phenotype, serving as an OA model. Furthermore, we tested different types of drugs, and the outcomes indicated that each tested drug was effective in alleviating OA using the OA-like cartilage-on-chip. Notably, the results obtained were consistent with in vivo findings, thereby validating the utility of the cartilage-on-chip as a reliable platform for drug screening. This study underscores the potential of organ-on-a-chip in advancing OA research and drug development, offering a more physiologically relevant and ethically sustainable alternative to traditional models to reduce costs and enhance efficiency.

Keywords
Osteoarthritis
Organ-on-a-chip
Cartilage
Drug screening
Funding
This work was supported by the Major Research plan of the National Natural Science Foundation of China (Grant No. 92249303), the Key Project of the National Natural Science Foundation of China (Grant No. 82230071), Fujian Provincial Natural Science Foundation of China (Grant No. 2024J01222), the Young Scientists Fund of the National Natural Science Foundation of China (Grant No. 82202674), and the Young Scientists Fund of the National Natural Science Foundation of China (Grant No. 82202334).
Conflict of interest
Jiacan Su is the Editor-in-Chief of this journal but was not in any way involved in the editorial and peer-review process conducted for this paper, directly or indirectly. Separately, the other authors declared that they have no known competing financial interests or personal relationships that could have influenced the work reported in this paper.
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