Organoids and Organ-On-Chip Models for COVID-19 Research and Its Application in Modernization of Traditional Chinese Medicine: Opportunities and Challenges

Hongda Sheng , Yingxin Liang , Volker M. Lauschke , Yi Wang

Engineering ›› 2025, Vol. 54 ›› Issue (11) : 171 -186.

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Engineering ›› 2025, Vol. 54 ›› Issue (11) :171 -186. DOI: 10.1016/j.eng.2025.01.019
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Organoids and Organ-On-Chip Models for COVID-19 Research and Its Application in Modernization of Traditional Chinese Medicine: Opportunities and Challenges
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Abstract

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), not only affects the lungs but also damages various non-pulmonary organs, resulting in tissue injury and potential long-term sequelae in infected individuals. COVID-19 is likely to persist as a public health concern, given the frequent emergence of new mutations and viral strains. Multiple clinical lines of evidence indicate the efficacy of traditional Chinese medicine (TCM) in the prevention and treatment of COVID-19. However, the exact mechanism underlying these effects remains unclear. In this perspective review, we summarize the utility of in vitro three-dimensional (3D) cultured organoid models and organ-on-a-chip (OoC) technology for studying COVID-19 pathogenesis, viral tropism, and infectious mechanisms across different tissues. We highlight the successful application of these platforms in aiding drug development and discuss their advantages and limitations. We also review how such organotypic models can be employed to study TCMs. Finally, we discuss the opportunities for integrated microphysiological multi-tissue models to rapidly discover active components and potential targets in the context of COVID-19. The utilization of these emerging technologies could accelerate drug discovery and the modernization of TCM.

Keywords

COVID-19 / Organoids / Organ-on-a-chip / Microphysiological systems / TCM

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Hongda Sheng, Yingxin Liang, Volker M. Lauschke, Yi Wang. Organoids and Organ-On-Chip Models for COVID-19 Research and Its Application in Modernization of Traditional Chinese Medicine: Opportunities and Challenges. Engineering, 2025, 54(11): 171-186 DOI:10.1016/j.eng.2025.01.019

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CRediT authorship contribution statement

Hongda Sheng: Writing – review & editing, Writing – original draft, Investigation, Data curation, Conceptualization. Yingxin Liang: Writing – review & editing, Writing – original draft, Data curation. Volker M. Lauschke: Writing – review & editing, Writing – original draft, Resources, Conceptualization. Yi Wang: Writing – review & editing, Resources, Funding acquisition, Conceptualization.

Declaration of competing interest

The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: [V.M.L. is co-founder and CEO of HepaPredict AB, as well as CSO of Shanghai Hepa Biotechnology, Co. Ltd.].

Acknowledgments

This study was supported by the Zhejiang Provincial Natural Science Foundation of China (LDT23H19012H19), the National Key R&D Program of China (2021YFC1712905). Yi Wang was supported by the Innovation Team and Talents Cultivation Program of National Administration of Traditional Chinese Medicine (ZYYCXTD-D-202002) and the Fundamental Research Funds for the Central Universities (226-2024-00001). Volker M. Lauschke was supported by the Swedish Research Council (2019-01837 and 2021-02801), Ruth och Richard Julins Foundation for Gastroenterology (2021-00158), the Knut and Alice Wallenberg Foundation (VC-2021-0026), and Robert Bosch Foundation, Stuttgart, Germany.

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