AccScience Publishing / IJB / Online First / DOI: 10.36922/ijb.5828
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RESEARCH ARTICLE

Ink comparison for extrusion-based bioprinting in the context of breast cancer and melanoma models

Stefanie Heltmann-Meyer1 ,  Stefan Fleischer1 ,  Sheetal Kadam1 ,  Aldo R. Boccaccini2 ,  Salvador Kirmsse1 ,  Leonard Forster3 ,  Jörg Teßmar3 ,  Stefan Schrüfer4 ,  Zan Lamberger5 ,  Philipp Stahlhut5 ,  Gregor Lang5 ,  Anja K. Boßerhoff6 ,  Andreas Arkudas1 ,  Raymund E. Horch1 ,  Annika Kengelbach-Weigand1 ,  Rafael Schmid1
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1 Department of Plastic and Hand Surgery, Laboratory for Tissue Engineering and Regenerative Medicine, University Hospital Erlangen, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
2 Institute of Biomaterials, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
3 Department of Functional Materials in Medicine and Dentistry at the Institute of Functional Materials and Biofabrication (IFB), University of Würzburg and KeyLab Polymers for Medicine of the Bavarian Polymer Institute (BPI), Würzburg, Germany
4 Institute of Polymer Materials, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
5 Department for Functional Materials in Medicine and Dentistry, University Hospital of Würzburg, Würzburg, Germany
6 Institute of Biochemistry, Friedrich-Alexander-University Erlangen-Nürnberg, Erlangen, Germany
IJB, 5828 https://doi.org/10.36922/ijb.5828
Submitted: 8 November 2024 | Accepted: 20 January 2025 | Published: 21 January 2025
(This article belongs to the Special Issue Bioprinting of in Vitro Tissue and Disease Models)
© 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution 4.0 International License ( https://creativecommons.org/licenses/by/4.0/ )
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Abstract

Biofabrication has proven to be a versatile and valuable tool for tissue engineering and cancer research, enabling the mimicry of various tumor microenvironments. In the present study, four different cell lines, including two melanoma cell lines, Mel Im and Mel Wei, and two breast cancer cell lines, MDA-MB-231 and MCF-7, were tested in combination with four distinct hydrogels. The hydrogels used were a composite ink of alginate, hyaluronic acid, and gelatin (Alg/HA/Gel), pre-crosslinked oxidized alginate with gelatin (ADA-GEL), alginate with methylcellulose (Meth-Alg), and acrylated hyaluronic acid (HAA). Rheological analysis, shear stress calculations, printability assays, and dynamic mechanical analysis were performed on all hydrogels. The cell lines were then mixed into the hydrogels, printed, and examined over 14 days, with a focus on cell survival, metabolic activity, and cell cycle analysis using fluorescent ubiquitination-based cell cycle indicator reporters. The results showed that all hydrogels were printable, with Meth-Alg being the softest gel. The cell lines survived the printing process in all bioinks, but there were significant differences in the metabolic activity and the predominant cell cycle stage. In Alg/HA/Gel, the cells grew in spheroid colonies. ADA-GEL proved to be a good bioink, supporting proliferation, migration, and high metabolic activity across all cell lines, while Meth- Alg offered pore structures conducive to cell spreading and proliferation. However, HAA resulted in the lowest cell number and metabolic activity across all cell lines, likely due to its high polymer content, which induced senescence. Our data demonstrated that each of these bioinks presents unique advantages for breast cancer and melanoma research models.

Graphical abstract
Keywords
Biofabrication
Bioink
Cell survival
Cell viability
Printability
Tumor
Funding
The research was funded by the Deutsche Forschungsgemeinschaft (DFG), German Research Foundation (Project number: 326998133, TRR 225; subprojects C03, A01, A02, A07, and C04).
Conflict of interest
Aldo R. Boccaccini and Raymund E. Horch serve as the Editorial Board Members of the journal, but did not in any way involve in the editorial and peer-review process conducted for this paper, directly or indirectly. Other authors declare they have no competing interests.
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International Journal of Bioprinting, Electronic ISSN: 2424-8002 Print ISSN: 2424-7723, Published by AccScience Publishing
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