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3D extrusion bioprinting

Abstract

Three-dimensional (3D) bioprinting strategies use computer-aided processes to enable automated simultaneous spatial patterning of cells and/or biomaterials. These technologies are suitable for a broad range of biomedical applications owing to their capability to produce structurally sophisticated and functionally relevant tissue constructs. Extrusion-based 3D bioprinting strategies were among the first modalities developed and are now arguably the most widely used for producing 3D tissue constructs. These technologies have rapidly evolved over the past two decades, providing a powerful tool set for the biofabrication of tissues that can facilitate translational efforts in the field. In this Primer, we describe the methodology of 3D extrusion bioprinting, focusing on the selection of hardware, software and bioinks. We expand upon recent advances in 3D extrusion bioprinting by illustrating the key variations that promote its biofabrication abilities. Finally, we provide an outlook on possible future refinements of the technology.

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Fig. 1: Extrusion bioprinting methods.
Fig. 2: Bioink designs.
Fig. 3: Variations on extrusion bioprinting strategies.
Fig. 4: Exemplary printability assessments.
Fig. 5: Shear stress assessment.
Fig. 6: In situ extrusion bioprinting strategies.
Fig. 7: Advances in extrusion (bio)printing methods.
Fig. 8: Artificial intelligence integration with extrusion (bio)printing methods.

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Acknowledgements

Y.S.Z. gratefully acknowledges funding from the NIH (R00CA201603, R21EB025270, R21EB026175, R21EB030257, R01EB028143 and R01HL153857), the National Science Foundation (CBET-EBMS-1936105) and the Brigham Research Institute. J.M. acknowledges support of the Gravitation Program ‘Materials Driven Regeneration’, funded by the Netherlands Organization for Scientific Research (024.003.013; J.M.).

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Introduction (Y.S.Z. and J.M.), Experimentation (Y.S.Z., G.H., J.M.L, M.C.M., W.Y.Y., M.Z-W. and J.M.), Results (Y.S.Z., J.M.L., W.Y.Y. and J.M.), Applications (Y.S.Z., D.J.K. and J.M.), Reproducibility and data deposition (Y.S.Z. and J.M.), Limitations and optimizations (Y.S.Z., T.H., M.L. and J.M.), Outlook (Y.S.Z., G.H., M.C.M. and J.M.). Overview of the Primer (Y.S.Z. and J.M.).

Corresponding author

Correspondence to Yu Shrike Zhang.

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Competing interests

Y.S.Z. sits on the Scientific Advisory Board of Allevi, Inc., which did not participate in this work or bias it in any form. This interest has been reviewed and managed by the Brigham and Women’s Hospital in accordance with its Conflict of Interest policies. M.C.M. serves on the Scientific Advisory Board and holds equity in GRIP Molecular Technologies. M.C.M. is Co-Founder and CSO of Flui3D, Inc. These interests have been reviewed and managed by the University of Minnesota in accordance with its Conflict of Interest policies. The other authors declare no competing interests.

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Nature Reviews Methods Primers thanks Nureddin Ashammakhi, Bige Deniz Unluturk, Wenguo Cui and the other, anonymous, reviewer(s) for their contribution to the peer review of this work.

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Supplementary information

Glossary

Shape fidelity

The degree to which the bioprinted structure conforms to the digital model.

Toolpath

The trajectory that the nozzle of the 3D bioprinter follows during bioink extrusion.

Infill density

The amount of material to be extruded for constructing the internal volume of a contruct, with 0% yielding a hollow shell structure (empty internally) and 100% yielding a full, solid object.

Shear rate

The rate of change in velocity at which one layer of fluid passes over an adjacent layer.

Amphiphiles

Molecules, either synthetic or natural, that contain both hydrophilic and hydrophobic domains.

Fugitive ink

An ink that serves as a temporary template after being printed, which can be subsequently selectively removed on demand to create a hollow space.

Computer vision

Machine learning or other artificial intelligence algorithms for processing and interpreting the visual data received from cameras or other vision systems, analogous to the human vision system and the brain.

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Zhang, Y.S., Haghiashtiani, G., Hübscher, T. et al. 3D extrusion bioprinting. Nat Rev Methods Primers 1, 75 (2021). https://doi.org/10.1038/s43586-021-00073-8

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