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and LGG-EVs. DS primarily exerts its effects by   in drug discovery but also offers a novel approach for
            inhibiting inflammatory pathways; HC-030031 alleviates   constructing in vitro disease models.
            inflammation and pain by blocking the TRPA1 channel;
            LGG-EVs promote cartilage repair by modulating immune   Acknowledgments
            and  inflammatory  responses.  The  experimental  results   The authors would like to thank Shanghai Tengyun
            demonstrated that all these drugs exhibited favorable   Biotechnology Co., Ltd. for developing the Hiplot Pro
            therapeutic effects in the cartilage organ-on-chip tests.   platform (https://hiplot.com.cn/) and providing technical
            These  findings  highlight that the  chip  platform  not only   assistance and valuable tools for data analysis and
            effectively assesses the efficacy of these different therapeutic   visualization.
            approaches  but  also  offers  significant advantages  in
            simulating  complex  pathological  environments  and  drug  Funding
            mechanisms of action. In addition, the platform can evaluate   This work was supported by the Major Research plan of
            the efficacy of drugs ranging from small-molecule chemical   the National Natural Science Foundation of China (Grant
            compounds (such as DS and HC-030031) to nanoscale   No.  92249303), the Key Project of the National Natural
            biopharmaceuticals (such as LGG-EVs), underscoring   Science Foundation of China (Grant No. 82230071), Fujian
            its broad applicability. In summary, the chip platform   Provincial Natural Science Foundation of China (Grant
            demonstrates considerable advantages in evaluating the   No. 2024J01222), the Young Scientists Fund of the National
            efficacy of drugs with varying sizes, compositions, and   Natural Science Foundation of China (Grant No. 82202674),
            mechanisms of action, providing strong technical support   and the Young Scientists Fund of the National Natural
            for the drug development of OA and other cartilage-related   Science Foundation of China (Grant No. 82202334).
            diseases. Therefore, based on the specific characteristics
            of  different  drugs,  we can further  optimize  the  platform   Conflict of interest
            by precisely simulating the pathological environment and
            adjusting the model structure, enabling the chip platform   Jiacan Su is the Editor-in-Chief of this journal but was not
            to better mimic the actual pathological structures. This   in any way involved in the editorial and peer-review process
            approach will enhance the accuracy and reliability of drug   conducted for this paper, directly or indirectly. Separately,
            screening.                                        the  other  authors  declared that  they have  no  known
                                                              competing financial interests or personal relationships that
               In summary, the cartilage-on-chip model introduces a   could have influenced the work reported in this paper.
            novel approach for OA research and material screening,
            showcasing  its  innovation  and  potential  application.  Author contributions
            Future studies can improve the model’s biocompatibility,   Conceptualization: Ke Xu, Jiacan Su
            stability, and precision by exploring new matrix materials   Formal analysis: Jian Wang, Miaomiao Wang, Fuxiao Wang
            and optimizing microfluidic technology. Furthermore,
            integrating the cartilage-on-chip with other organs-  Investigation: Jing Zhao, Fuming Shen, Shihao Sheng
            on-chip  can  create a  human-on-a-chip platform  to   Methodology: Yingying Jiang, Yingying Jing
            study interactions between various organs. Continuous   Writing – original draft: Jing Zhao, Fuming Shen, Shihao
                                                                 Sheng
            technological  innovation  and    interdisciplinary  Writing – review & editing: Ke Xu, Jiacan Su
            collaboration can enhance the model’s utility and accuracy,
            providing a strong foundation for developing effective OA   Ethics approval and consent to participate
            treatments and strategies.
                                                              Not applicable.
            5. Conclusion

            This study presents an innovative cartilage-on-a-  Consent for publication
            chip platform designed to mimic the pathological   Not applicable.
            microenvironment of OA for drug screening purposes. By   Availability of data
            integrating microfluidics and cartilage tissue engineering,
            the platform successfully replicates ECM degradation and   The data that support the findings of this study are available
            inflammatory responses observed in OA conditions. The   from the corresponding authors upon reasonable request.
            experimental results demonstrate the platform’s efficiency
            in evaluating the protective effects of candidate drugs on   References
            cartilage tissue, providing a reliable and high-throughput   1.   Xie R, Pal V, Yu Y,  et al. A  comprehensive review on 3D
            tool for OA drug development. This research not only   tissue models: Biofabrication technologies and preclinical
            highlights the potential of cartilage-on-a-chip systems   applications. Biomaterials. 2024;304:122408.


            Volume 1 Issue 1 (2025)                         17                                doi: 10.36922/or.8461
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