Page 402 - IJB-10-2

International Journal of Bioprinting Automated bioink mixer improves bioprinting

it is possible to make adjustments according to the prior homogeneity and cell viability. The results reveal that the
experiment result. Conversely, more precise and accurate mixing speed has a more pronounced impact on these
control of these parameters can bring more reproducible parameters than the mixing number. The study also
results and greatly simplify the optimization process. highlighted the importance of standardizing the bioink
Finally, a positive feedback loop, which is very effective for mixing process for 3D bioprinting. By using a machine
the optimization of experimental conditions, is formed. for bioink mixing, notable improvements were observed
Once the parameters have been determined, the conditions in bioink homogeneity, cell distribution, cell viability, and
can be precisely reproduced in subsequent experiments. rheological properties compared to human mixing, which
Hence, this is considered an effective step to enhance the was characterized by strong inter-individual variations,
consistency and repeatability of the 3D bioprinting results. as well as variability among independent experiments
carried out by the same operator. These findings strongly
Importantly, the strategy and methodology of this study
is readily scalable and popularized for relevant applications suggest that the standardization of bioink mixing process
using an automated device is instrumental for substantially
in this field. Li et al. built an automated active mixing enhancing the reproducibility and reliability of 3D
49
platform adapted from syringe pumps that can prepare bioprinting experiments. Furthermore, automated mixing
homogeneous hydrogel bioinks automatically, yielding of hydrogels will also contribute to improvements of the
results consistent with ours. Nonetheless, the developed experimental outcome in related areas such as 3D cell
platform still exhibits some limitations, especially culture, organoid research, and stem cell cultivation. The
regarding the different syringe compatibility, convenience American folk hero John Henry won the contest against
on changing mixture volume, and large-space occupation. the steam-powered rock drilling machine with his hammer
Here, we provide a rational design of the automated but died doing so. Just a few years later, no one called into
device, which is more compatible, maneuverable, reliable, question whether machines were faster. Nowadays, it is
and compact in size. Various volumes/volume ratios and obvious that automatization is necessary to improve the
standard/customized couplers can be easily handled due quality of precision research.
to the readily adjustable rack structure and barrel-moving
design. Syringes from different manufacturers can also Acknowledgments
be used by simply switching the endstop adaptors. The
involved hardware is easily accessible and ordinary in We are thankful to Erik Wade for proofreading and
common automation equipment, such as 3D printers, valuable discussion.
automatic loading devices, and robotics. 50-53 Therefore, we
believe that this strategy can not only effectively improve Funding
the cell status and bioink homogeneity, but also contribute This research was supported by the Chinese Scholarship
to the situations of mixing spheroids, growth factors, Council (CSC; fellowship No. 201906780024 to D.W., and
54
55
drugs, pigment, nanoparticles, 58,59 etc. This could fellowship No. 201906780023 to S.P.). Financial support
57
56
facilitate the 3D bioprinting research and also benefit the from the Einstein Foundation Berlin (Einstein Center 3R,
related areas. EZ-2020-597-2) is gratefully acknowledged.
Future research should focus on exploring additional
mixing parameters to further optimize the bioink mixing Conflict of interest
process. These parameters may include temperature The authors declare no conflicts of interest.
control, motion acceleration and deceleration control,
and more complex mixing programs with varying mixing Author contributions
periods. Exploring various cell densities, additional
hydrogel candidates, and different bioink forms (e.g., Conceptualization: Jens Kurreck, Dongwei Wu, Shumin
microgels, cell aggregates) is also of interest. This Pang, Ahmed S. M. Ali
comprehensive approach would contribute to enhancing Data curation: Dongwei Wu, Shumin Pang, Ahmed S. M.
Ali, Yikun Mei, Viola Röhrs
the reproducibility and quality of bioink preparation in Formal analysis: Jens Kurreck, Dongwei Wu, Shumin Pang,
various applications of 3D bioprinting.
Viola Röhrs, Johanna Berg, Ahmed S. M. Ali, Yikun
5. Conclusion Mei, Mathias Ziersch, Beatrice Tolksdorf
Funding acquisition: Jens Kurreck, Johanna Berg
In conclusion, this study systematically investigated Methodology: Jens Kurreck, Dongwei Wu, Shumin Pang,
the effects of various mixing parameters, particularly Ahmed S. M. Ali
the mixing speed and the mixing number, on bioink Resources: Jens Kurreck, Johanna Berg

Volume 10 Issue 2 (2024) 394 doi: 10.36922/ijb.1974