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Organ-on-chip models for infectious disease research

Nature Microbiology volume 9, pages 891–904 (2024)Cite this article

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Abstract

Research on microbial pathogens has traditionally relied on animal and cell culture models to mimic infection processes in the host. Over recent years, developments in microfluidics and bioengineering have led to organ-on-chip (OoC) technologies. These microfluidic systems create conditions that are more physiologically relevant and can be considered humanized in vitro models. Here we review various OoC models and how they have been applied for infectious disease research. We outline the properties that make them valuable tools in microbiology, such as dynamic microenvironments, vascularization, near-physiological tissue constitutions and partial integration of functional immune cells, as well as their limitations. Finally, we discuss the prospects for OoCs and their potential role in future infectious disease research.

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Fig. 1: Common OoC models.
Fig. 2: OoC models in infection biology.
Fig. 3: Exemplary OoC models used in infectious disease research.
Fig. 4: Integrating functional immune cells in OoC models.

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Acknowledgements

This work was funded by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) under Germany’s Excellence Strategy (EXC 2051, Project-ID 390713860). R.A.-R., A.S.M., M.T.F., F.H.S., C.E., K.P. and B.H. are supported by the DFG Cluster of Excellence ‘Balance of the Microverse’. R.A.-R. acknowledges project funding from the Carl Zeiss Foundation. A.S.M. has received funding from the Innovative Medicines Initiative 2 Joint Undertaking under grant agreement 101007799 (Inno4Vac). This joint undertaking receives support from the European Union’s Horizon 2020 research and innovation programme and European Federation of Pharmaceutical Industries and Associations (EFPIA). A.S.M. is further supported by the DFG Priority Programme SPP 2332 ‘Physics of Parasitism’, by the Leibniz ScienceCampus InfectoOptics Jena, which is financed by the funding line Strategic Networking of the Leibniz Association, and the Federal Ministry of Education and Research (Bundesministerium für Bildung und Forschung; BMBF) funding programme Photonics Research Germany (FKZ: 13N15716) which is integrated into the Leibniz Center for Photonics in Infection Research (LPI). The LPI initiated by Leibniz-Institute of Photonic Technology (IPHT), Leibniz-Hans-Knöll-Institute (Leibniz-HKI), Jena University Hospital (Uniklinikum Jena; UKJ) and Friedrich-Schiller-University (FSU) Jena is part of the BMBF national roadmap for research infrastructures. M.S.G. was supported by the DFG Emmy Noether programme (project 434385622/GR 5617/1-1). M.T.F. received funding from the German Federal Ministry of Education and Research within the funding programme Photonics Research Germany, Project Leibniz Center for Photonics in Infection Research, Subproject LPI-BT3, contract number 13N15709. M.T.F. was further supported by the Leibniz ScienceCampus InfectoOptics Jena (PNEUTHERA project), which is financed by the funding line Strategic Networking of the Leibniz Association. B.H. is further supported by the DFG Priority Programme SPP 2225 ‘Exit strategies of intracellular pathogens’, the DFG project Hu 532/20-1, the European Union Horizon 2020 grant agreement 847507 (HDM-FUN) and the Marie Sklodowska-Curie grant agreement 812969 (FunHoMic), and the Leibniz Association Campus InfectoOptics SAS-2015-HKI-LWC. M.S.G., M.T.F. and B.H. are further supported by the DFG Collaborative Research Centre (CRC)/Transregio (TRR) 124 FungiNet with project number 210879364 (subprojects B4, C1 and C2). M.T.F. was further supported by the DFG Collaborative Research Centre CRC 1278 ‘PolyTarget’ (project 316213987, subproject Z01). K.P. also acknowledges support from the DFG Priority Programme SPP2389 ‘Emergent Functions of Bacterial Multicellularity’. F.H.S. is further supported by the DFG Collaborative Research Centre CRC 1278 ‘PolyTarget’ (project 316213987, projects A03 and B04), by the DFG Priority Programme SPP 2332 ‘Physics of Parasitism’ (project 491921522), and the research unit 2811 (project 397384169, project TP02). C.E. acknowledges support by the Microverse Imaging Center (A. Jost, P. Then, S. Neumann and G. Zhurgenbayeva) and further funding by the DFG (project 316213987 – SFB 1278 (projects A04, D01, Z01); and project PolaRas EG 325/2-1;), Free State of Thuringia (TAB; AdvancedSTED/FGZ: 2018 FGI 0022; Advanced Flu-Spec/2020 FGZ: FGI 0031), the Leibniz ScienceCampus InfectoOptics Jena (project PNEUTHERA, funding line Strategic Networking of the Leibniz Association), and the BMBF funding programme Photonics Research Germany (FKZ: 13N15716), which is integrated into the Leibniz Center for Photonics in Infection Research (LPI). The LPI initiated by Leibniz-IPHT, Leibniz-HKI, UKJ and FSU Jena is part of the BMBF national roadmap for research infrastructures.

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Authors and Affiliations

  1. Department of Microbial Pathogenicity Mechanisms, Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute (Leibniz-HKI), Jena, Germany

    Raquel Alonso-Roman & Bernhard Hube

  2. Cluster of Excellence Balance of the Microverse, Friedrich Schiller University Jena, Jena, Germany

    Raquel Alonso-Roman, Alexander S. Mosig, Marc Thilo Figge, Kai Papenfort, Christian Eggeling, Felix H. Schacher, Bernhard Hube & Mark S. Gresnigt

  3. Institute of Biochemistry II, Jena University Hospital, Jena, Germany

    Alexander S. Mosig

  4. Center for Sepsis Control and Care, Jena University Hospital, Friedrich-Schiller University, Jena, Germany

    Alexander S. Mosig

  5. Applied Systems Biology Group, Leibniz-HKI, Jena, Germany

    Marc Thilo Figge

  6. Institute of Microbiology, Faculty of Biological Sciences, Friedrich Schiller University, Jena, Germany

    Marc Thilo Figge, Kai Papenfort & Bernhard Hube

  7. Leibniz Institute of Photonic Technology, Leibniz Center for Photonics in Infection Research e.V., Jena, Germany

    Christian Eggeling

  8. Institute of Applied Optics and Biophysics, Friedrich Schiller University Jena, Jena, Germany

    Christian Eggeling

  9. Jena Center for Soft Matter, Jena, Germany

    Christian Eggeling & Felix H. Schacher

  10. Institute of Organic Chemistry and Macromolecular Chemistry, Friedrich Schiller University, Jena, Germany

    Felix H. Schacher

  11. Junior Research Group Adaptive Pathogenicity Strategies, Leibniz-HKI, Jena, Germany

    Mark S. Gresnigt

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Contributions

R.A.-R. was responsible for conceptualization, literature research, writing and editing the manuscript, and preparing figures. A.S.M., M.T.F., C.E. and F.H.S. were responsible for writing sections of the manuscript and editing the manuscript. K.P. was responsible for editing the manuscript. B.H. was responsible for conceptualization, supervision and editing the manuscript. M.S.G. was responsible for conceptualization, supervision, writing sections of the manuscript, editing the manuscript, and preparing figures.

Corresponding author

Correspondence to Bernhard Hube.

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Competing interests

A.S.M. consults for and holds equity in Dynamic42 GmbH. R.A.-R., M.T.F., M.S.G. and B.H. are members of the Leibniz Institute for Natural Product Research and Infection Biology - Hans-Knöll-Institute (Leibniz-HKI), which holds a cooperation agreement with Dynamic42 GmbH. The Leibniz-HKI is also member of the EU consortium FunHoMic, which maintains a consortium agreement and includes the company Mimetas. The other authors declare no competing interests.

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Alonso-Roman, R., Mosig, A.S., Figge, M.T. et al. Organ-on-chip models for infectious disease research. Nat Microbiol 9, 891–904 (2024). https://doi.org/10.1038/s41564-024-01645-6

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