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ORIGINAL RESEARCH ARTICLE
Cartilage-on-chip for osteoarthritis drug screening

Jing Zhao 1,2,3† , Fuming Shen 1,2,3† , Shihao Sheng , Jian Wang 1,2,3 , Miaomiao Wang 1,2 , Fuxiao Wang 1,2 ,
4†
Yingying Jiang 1,2 , Yingying Jing , Ke Xu 1,2,5,6,7 * , and Jiacan Su 1,2,4,5,6,7 *
1,2
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.
*Corresponding authors: Ke Xu (kexu@shu.edu.cn); Jiacan Su (jiacansu@shu.edu.cn)

Citation: Zhao J, Shen F, Sheng S, Abstract
et al. Cartilage-on-chip for
osteoarthritis drug screening.
Organoid Res. 2025;1(1):8461. Osteoarthritis (OA) is a common disease characterized by degenerative changes
doi: 10.36922/or.8461 in joint cartilage, manifesting clinically as joint pain, stiffness, and functional
impairment. At present, the variety of drugs available for OA is relatively limited,
Received: January 8, 2025
and these primarily serve to alleviate symptoms rather than effectuate actual
Revised: March 3, 2025 cartilage repair. The complex cellular environment and biochemical reactions
Accepted: March 7, 2025 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
Published online: March 25, 2025
to mimic the microenvironment and physiological functions of human organs.
Copyright: © 2025 Author(s). This Herein, we developed a cartilage-on-chip by culturing primary chondrocytes in
is an Open-Access article distributed
under the terms of the Creative three dimensions within a microfluidic system. This novel design could maintain
Commons Attribution License, the cartilage phenotype and replicate its microenvironment. This cartilage-on-chip
permitting distribution, and reproduction cultured under interleukin-1 beta for 3 days displayed a distinct OA-like phenotype,
in any medium, which provided that the
original work is properly cited. 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
Publisher’s Note: AccScience
Publishing remains neutral with regard the OA-like cartilage-on-chip. Notably, the results obtained were consistent with
to jurisdictional claims in published in vivo findings, thereby validating the utility of the cartilage-on-chip as a reliable
maps and institutional affiliations. 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

1. Introduction During the pathological progression of OA, the cartilage
undergoes degenerative changes, including wear, tear,
Osteoarthritis (OA) is a persistent joint disorder influenced
by aging, genetic predisposition, and lifestyle factors. It and loss of elasticity. These changes not only lead to joint
is mainly distinguished by the gradual degradation of pain, stiffness, and limited function but also accelerate the
2
articular cartilage, the smooth connective tissue that coats degeneration of other joint tissues. Research indicates that
the ends of bones within joints. Serving as a cushion, understanding and controlling the mechanisms behind
cartilage primarily functions to reduce friction between cartilage degeneration is crucial for the treatment or delay
bones, thereby facilitating smooth joint movement. of OA. At present, pharmacotherapy is one of the primary
1

Volume 1 Issue 1 (2025) 1 doi: 10.36922/or.8461