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Fabrication of three-dimensional islet models by the geometry-controlled hanging-drop method

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Abstract

The hanging-drop method has been widely used to fabricate three-dimensional (3D) in vitro tissue models due to its advantages such as being easy to perform, inexpensive, and permitting precise control of cell spheroid formation. The geometry of hanging drop may play a critical role on the formation of cell spheroids, which, however, has not been explored. In this study, we developed a modified hanging-drop platform that enables the production of cell spheroids in a high-throughput manner by controlling hanging drop geometry with a defined spreading ring. The surface tension force is proportional to the spreading ring and the gravitational force is determined by droplet volume, and the geometry can be determined by the balance between surface tension and gravity. β-TC-6 cell spheroids with optimized diameters were fabricated as 3D in vitro islet models. The models showed morphology similar to primary islets and had functionality that more closely resembled primary islets than two-dimensional cell culture. The developed platform holds great potential for engineering well-controlled in vitro tissue models for various applications such as physiological and pathological studies, drug screening, as well as transplantation for treatment purpose.

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Acknowledgements

This work was financially supported by the National Natural Science Foundation of China (Grants 51605377 and 81300696) and the Natural Science Foundation of Shaanxi Province (Grant 2017JQ5004).

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Authors and Affiliations

  1. Department of Endocrinology and Metabolism, The First Affiliated Hospital, Air Force Military Medical University, Xi’an, 710032, China

    Bin Gao

  2. Outpatient Department of Lanzhou Military Region, 940 Hospital, Joint Logistics Support Force of the People’s Liberation Army of China, Lanzhou, 730000, China

    Ce Jing

  3. Department of Biomedical Engineering, Faculty of Engineering, University of Malaya, 50603, Kuala Lumpur, Malaysia

    Kelvin Ng & Belinda Pingguan-Murphy

  4. Key Laboratory of Biomedical Information Engineering of Ministry of Education, School of Life Science and Technology, Xi’an Jiaotong University, Xi’an, 710049, China

    Qingzhen Yang

  5. Bioinspired Engineering and Biomechanics Center (BEBC), Xi’an Jiaotong University, Xi’an, 710049, China

    Qingzhen Yang

Authors
  1. Bin Gao
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  2. Ce Jing
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  3. Kelvin Ng
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  5. Qingzhen Yang
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Correspondence to Qingzhen Yang.

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Gao, B., Jing, C., Ng, K. et al. Fabrication of three-dimensional islet models by the geometry-controlled hanging-drop method. Acta Mech. Sin. 35, 329–337 (2019). https://doi.org/10.1007/s10409-019-00856-z

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  • DOI: https://doi.org/10.1007/s10409-019-00856-z

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