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International

                                                                         Journal of Bioprinting



                                        RESEARCH ARTICLE
                                        Man vs. machine: Automated bioink mixing

                                        device improves reliability and reproducibility
                                        of bioprinting results compared to human

                                        operators



                                        Dongwei Wu , Shumin Pang , Viola Röhrs , Johanna Berg , Ahmed S. M. Ali ,
                                                   1
                                                                2
                                                                                          1
                                                                                                         1
                                                                            1
                                        Yikun Mei , Mathias Ziersch , Beatrice Tolksdorf , and Jens Kurreck *
                                                                1
                                                 1
                                                                                                  1
                                                                                  1
                                        1 Chair  of Applied  Biochemistry, Institute of Biotechnology,  Technische  Universität Berlin,  Berlin,
                                        Germany
                                        2 Chair of Advanced Ceramic Materials, Institute of Material Science and Technology, Technische
                                        Universität Berlin, Berlin, Germany
                                        Abstract
                                        The bioink mixing process is highly relevant to the bioink quality, which is the
                                        basis for reproducible extrusion-based three-dimensional (3D) bioprinting (EBB).
                                        Currently, most bioinks mixed by skilled human operators show variations in terms
                                        of cell homogeneity and biological properties as well as other properties. For
                                        preparation of many types of bioinks, striking the balance between homogeneity
                                        and cell viability remains a major challenge. This study investigates the relationship
                                        between bioink homogeneity and mixing parameters, particularly mixing speed and
                                        number of exchanges, utilizing a customized automated device. We found that up to
            *Corresponding author:      a certain point, increasing the rate of mixing led to a better distribution of cells within
            Jens Kurreck                the bioink, but beyond that point, there was a detrimental effect on cell viability. In
            (jens.kurreck@tu-berlin.de)
                                        contrast, the mixing number had less impact on the physiological properties of the
            Citation: Wu D, Pang S, Röhrs V,   cells in the bioink. Furthermore, a comparison between skilled human and machine
            et al. Man vs. machine: Automated   bioink mixing revealed that the machine consistently provided better outcomes
            bioink mixing device improves
            reliability and reproducibility of   in terms of bioink homogeneity, cell distribution,  and cell viability, highlighting
            bioprinting results compared to   the advantages and importance of standardizing the bioink mixing process. The
            human operators. Int J Bioprint.   methodology and approaches in this study can improve the reproducibility and
            2024;10(2):1974.
            doi: 10.36922/ijb.1974      reliability of EBB bioink and may thereby advance the field of 3D bioprinting in
                                        various applications.
            Received: October 5, 2023
            Accepted: December 14, 2023
            Published Online: February 12, 2024
                                        Keywords: Bioink; Hydrogel mixing; Mixing device; Bioprinting; Homogeneity;
            Copyright: © 2024 Author(s).   Cell viability
            This is an Open Access article
            distributed under the terms of the
            Creative Commons Attribution
            License, permitting distribution,
            and reproduction in any medium,   1. Introduction
            provided the original work is
            properly cited.             Bioprinting has become a widely used technology in various fields of biomedical
                                               1-3
            Publisher’s Note: AccScience   research.  Among the different methodologies, extrusion-based bioprinting (EBB) has
            Publishing remains neutral with   become the most widely used approach.  This is primarily attributed to its affordability
                                                                        4,5
            regard to jurisdictional claims in
            published maps and institutional   and maneuverability, which allow for the creation of intricate three-dimensional (3D)
            affiliations.               structures that closely resemble the architecture and microenvironment of native tissues.

            Volume 10 Issue 2 (2024)                       380                                doi: 10.36922/ijb.1974
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