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A covalently crosslinked bioink for multi-materials drop-on-demand 3D bioprinting of three-dimensional cell cultures

Robert H. Utama, Vincent T. G. Tan, Kristel C. Tjandra, Andrew Sexton, Duyen H. T. Nguyen, Aidan P. O’Mahony, Julio C. C. Ribeiro, View ORCID ProfileMaria Kavallaris, J. Justin Gooding
doi: https://doi.org/10.1101/2021.02.18.431759
Robert H. Utama
1School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
3Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia
4ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW 2052, Australia
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Vincent T. G. Tan
1School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
3Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia
4ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW 2052, Australia
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Kristel C. Tjandra
1School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
3Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia
4ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW 2052, Australia
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Andrew Sexton
5Inventia Life Science Pty Ltd, Sydney, New South Wales, Australia
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Duyen H. T. Nguyen
1School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
3Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia
4ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW 2052, Australia
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Aidan P. O’Mahony
5Inventia Life Science Pty Ltd, Sydney, New South Wales, Australia
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Julio C. C. Ribeiro
5Inventia Life Science Pty Ltd, Sydney, New South Wales, Australia
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Maria Kavallaris
2Children’s Cancer Institute, Lowy Cancer Research Centre, The University of New South Wales, Sydney, NSW 2052, Australia
3Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia
4ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW 2052, Australia
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  • ORCID record for Maria Kavallaris
J. Justin Gooding
1School of Chemistry, The University of New South Wales, Sydney, NSW 2052, Australia
3Australian Centre for NanoMedicine, The University of New South Wales, Sydney, NSW 2052, Australia
4ARC Centre of Excellence in Convergent Bio-Nano Science and Technology, The University of New South Wales, Sydney, NSW 2052, Australia
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  • For correspondence: justin.gooding@unsw.edu.au
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Abstract

In vitro three-dimensional (3D) cell models have been accepted to better recapitulate aspects of in vivo organ environment than 2D cell culture. Currently, the production of these complex in vitro 3D cell models with multiple cell types and microenvironments remains challenging and prone to human error. Here we report a versatile bioink comprised of a 4-arm PEG based polymer with distal maleimide derivatives as the main ink component and a bis-thiol species as the activator that crosslinks the polymer to form the hydrogel in less than a second. The rapid gelation makes the polymer system compatible with 3D bioprinting. The ink is combined with a drop-on-demand 3D bioprinting platform consisting of eight independently addressable nozzles and high-throughput printing logic for creating complex 3D cell culture models. The combination of multiple nozzles and fast printing logic enables the rapid preparation of many complex 3D structures comprising multiple hydrogel environments in the one structure in a standard 96-well plate format. The platform compatibility for biological applications was validated using pancreatic ductal adenocarcinoma cancer (PDAC) cells with their phenotypic responses controlled by tuning the hydrogel microenvironment.

Competing Interest Statement

A.P.O.M., A.S., and J.C.C.R. are consultants, employees, shareholders and/or optionees of Inventia Life Science Pty Ltd. Inventia has an interest in commercializing the 3D bioprinting technology.

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The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted February 18, 2021.
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A covalently crosslinked bioink for multi-materials drop-on-demand 3D bioprinting of three-dimensional cell cultures
Robert H. Utama, Vincent T. G. Tan, Kristel C. Tjandra, Andrew Sexton, Duyen H. T. Nguyen, Aidan P. O’Mahony, Julio C. C. Ribeiro, Maria Kavallaris, J. Justin Gooding
bioRxiv 2021.02.18.431759; doi: https://doi.org/10.1101/2021.02.18.431759
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A covalently crosslinked bioink for multi-materials drop-on-demand 3D bioprinting of three-dimensional cell cultures
Robert H. Utama, Vincent T. G. Tan, Kristel C. Tjandra, Andrew Sexton, Duyen H. T. Nguyen, Aidan P. O’Mahony, Julio C. C. Ribeiro, Maria Kavallaris, J. Justin Gooding
bioRxiv 2021.02.18.431759; doi: https://doi.org/10.1101/2021.02.18.431759

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