Man vs. machine: Automated bioink mixing device improves reliability and reproducibility of bioprinting results compared to human operators

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 a certain point, increasing the rate of mixing led to a better distribution of cells within the bioink, but beyond that point, there was a detrimental effect on cell viability. In contrast, the mixing number had less impact on the physiological properties of the cells in the bioink. Furthermore, a comparison between skilled human and machine bioink mixing revealed that the machine consistently provided better outcomes in terms of bioink homogeneity, cell distribution, and cell viability, highlighting the advantages and importance of standardizing the bioink mixing process. The methodology and approaches in this study can improve the reproducibility and reliability of EBB bioink and may thereby advance the field of 3D bioprinting in various applications.