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Spheroid construction strategies and application in 3D bioprinting

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Abstract

Tissue engineering has been striving toward designing and producing natural and functional human tissues. Cells are the fundamental building blocks of tissues. Compared with traditional two-dimensional cultured cells, cell spheres are three-dimensional (3D) structures that can naturally form complex cell–cell and cell–matrix interactions. This structure is close to the natural environment of cells in living organisms. In addition to being used in disease modeling and drug screening, spheroids have significant potential in tissue regeneration. The 3D bioprinting is an advanced biofabrication technique. It accurately deposits bioinks into predesigned 3D shapes to create complex tissue structures. Although 3D bioprinting is efficient, the time required for cells to develop into complex tissue structures can be lengthy. The 3D bioprinting of spheroids significantly reduces the time required for their development into large tissues/organs during later cultivation stages by printing them with high cell density. Combining spheroid fabrication and bioprinting technology should provide a new solution to many problems in regenerative medicine. This paper systematically elaborates and analyzes the spheroid fabrication methods and 3D bioprinting strategies by introducing spheroids as building blocks. Finally, we present the primary challenges faced by spheroid fabrication and 3D bioprinting with future requirements and some recommendations.

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Fig. 1
Fig. 2
Fig. 3

Reproduced from Ref. [95], Copyright 2019, with permission from Society for Laboratory Automation and Screening

Fig. 4

Reproduced from Ref. [97], Copyright 2021, with permission from the authors, licensed under the Creative Commons Attribution 4.0 license

Fig. 5

Reproduced from Ref. [99], Copyright 2018, with permission from WILEY–VCH Verlag GmbH & Co. KGaA, Weinheim. d The spheroids are picked from the cell media by a glass pipette, where the required back pressure is set to lift the spheroids. e, e1 A schematic showing critical parameters during bioprinting; e2–e8 spheroids are printed at the desired locations. Reproduced from Ref. [100], Copyright 2020, with permission from the authors, licensed under CC BY-NC

Fig. 6

Reproduced from Ref. [138], Copyright 2013, with permission from Acta Materialia Inc. c, c1 The cells mixing with magnetic nanoparticles were then printed for 15 min by placing the plate on top of a 96-well magnetic drive; c2 spheroid contraction over 6 h as cells rearrange and compact (nuclei blue); c3 the mobile device based imaging system. Reproduced from Ref. [101], Copyright 2015, with permission from the authors, licensed under a Creative Commons Attribution 4.0 International License

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Acknowledgements

This work was supported by the National Natural Science Foundation of China (Nos. 61973206, 61703265, 61803250, and 61933008), the Shanghai Science and Technology Committee Rising-Star Program (No. 19QA1403700), and the National Center for Translational Medicine (Shanghai) SHU Branch.

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  1. School of Mechatronic Engineering and Automation, Shanghai University, Shanghai, 200444, China

    Chunxiang Lu, Chuang Gao, Hao Qiao, Yi Zhang, Aoxiang Jin & Yuanyuan Liu

  2. School of Medicine, Shanghai University, Shanghai, 200444, China

    Huazhen Liu

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CXL investigated and summarized the literature, and wrote the original draft. CG conducted deep review and editing. HQ and AXJ edited the images. YZ and HZL gave some advice. YYL helped revise the paper, supervised the work, and applied for funds. All authors have read and approved this manuscript for publication.

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Lu, C., Gao, C., Qiao, H. et al. Spheroid construction strategies and application in 3D bioprinting. Bio-des. Manuf. (2024). https://doi.org/10.1007/s42242-024-00273-7

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