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Vascularized organoid-on-a-chip: design, imaging, and analysis

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Abstract

Vascularized organoid-on-a-chip (VOoC) models achieve substance exchange in deep layers of organoids and provide a more physiologically relevant system in vitro. Common designs for VOoC primarily involve two categories: self-assembly of endothelial cells (ECs) to form microvessels and pre-patterned vessel lumens, both of which include the hydrogel region for EC growth and allow for controlled fluid perfusion on the chip. Characterizing the vasculature of VOoC often relies on high-resolution microscopic imaging. However, the high scattering of turbid tissues can limit optical imaging depth. To overcome this limitation, tissue optical clearing (TOC) techniques have emerged, allowing for 3D visualization of VOoC in conjunction with optical imaging techniques. The acquisition of large-scale imaging data, coupled with high-resolution imaging in whole-mount preparations, necessitates the development of highly efficient analysis methods. In this review, we provide an overview of the chip designs and culturing strategies employed for VOoC, as well as the applicable optical imaging and TOC methods. Furthermore, we summarize the vascular analysis techniques employed in VOoC, including deep learning. Finally, we discuss the existing challenges in VOoC and vascular analysis methods and provide an outlook for future development.

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Acknowledgements

This work was supported by the National Key Research and Development Program of China (Grant No. 2017YFA0700501); the National Natural Science Foundation of China (Grant Nos. 61860206009, 62375096, 82361138569, 82372012); the Key Research and Development Project of Hubei Province (Grant No. 2022BCA023); and the Open Research Fund of WNLO (Grant No. 2022WNLOKF009); the Open Competition Project of Wuhan East Lake High-tech Development Zone (Grant Nos. 2023KJB224, 2023KJB213).

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  1. Tingting Yu and Qihang Yang have contributed equally to this study.

Authors and Affiliations

  1. Britton Chance Center for Biomedical Photonics - MoE Key Laboratory for Biomedical Photonics, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China

    Tingting Yu, Qihang Yang & Dan Zhu

  2. Wuhan National Laboratory for Optoelectronics - Advanced Biomedical Imaging Facility, Huazhong University of Science and Technology, Wuhan, Hubei, 430074, China

    Tingting Yu, Qihang Yang & Dan Zhu

  3. Frontiers Science Center for Flexible Electronics, Xi’an Institute of Flexible Electronics (IFE) and Xi’an Institute of Biomedical Materials & Engineering, Northwestern Polytechnical University, Xi’an, Shanxi, 710072, China

    Bo Peng

  4. State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing, Jiangsu, 210096, China

    Zhongze Gu

  5. Institute of Biomaterials and Medical Devices, Southeast University, Suzhou, Jiangsu, 215163, China

    Zhongze Gu

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  1. Tingting Yu
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TY: Conceptualization; funding acquisition; visualization; writing—original draft; writing—review and editing of the manuscript. QY: Conceptualization; visualization; writing—original draft; writing—review and editing of the manuscript. Bo Peng: Funding acquisition; writing—review and editing of the manuscript. ZG: Supervision; writing—review and editing of the manuscript. DZ: conceptualization; funding acquisition; supervision; writing—review and editing of the manuscript.

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Yu, T., Yang, Q., Peng, B. et al. Vascularized organoid-on-a-chip: design, imaging, and analysis. Angiogenesis 27, 147–172 (2024). https://doi.org/10.1007/s10456-024-09905-z

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