Centre for Translational Bone, Joint and Soft Tissue Research, University Hospital Carl Gustav Carus, Faculty of Medicine, Technische Universität Dresden, Germany. Institute of Natural Materials Technology, Faculty of Mechanical Engineering, Technische Universität Dresden, Germany.
Biofabrication. 2020 Mar 11;12(2):025022. doi: 10.1088/1758-5090/ab7553.
Systematic analysis of the extrusion process in 3D bioprinting is mandatory for process optimization concerning production speed, shape fidelity of the 3D construct and cell viability. In this study, we applied numerical and analytical modeling to describe the fluid flow inside the printing head based on a Herschel-Bulkley model. The presented analytical calculation method nicely reproduces the results of Computational Fluid Dynamics simulation concerning pressure drop over the printing head and maximal shear parameters at the outlet. An approach with dimensionless flow parameter enables the user to adapt rheological characteristics of a bioink, the printing pressure and needle diameter with regard to processing time, shear sensitivity of the integrated cells, shape fidelity and strand dimension. Bioinks consist of a blend of polymers and cells, which lead to a complex fluid behavior. In the present study, a bioink containing alginate, methylcellulose and agarose (AMA) was used as experimental model to compare the calculated with the experimental pressure gradient. With cultures of an immortalized human mesenchymal stem cell line and plant cells (basil) it was tested how cells influence the flow and how mechanical forces inside the printing needle affect cell viability. Influences on both sides increased with cell (aggregation) size as well as a less spherical shape. This study contributes to a systematic description of the extrusion-based bioprinting process and introduces a general strategy for process design, transferable to other bioinks.
为了优化生产速度、3D 构建的形状保真度和细胞活力，对 3D 生物打印中的挤出过程进行系统分析是强制性的。在这项研究中，我们应用数值和分析建模来描述基于赫谢尔-布尔克利模型的打印头内部的流体流动。所提出的分析计算方法很好地再现了计算流体动力学模拟在打印头压降和出口处最大剪切参数方面的结果。无量纲流动参数的方法使用户能够适应生物墨水的流变特性、打印压力和针头直径，以考虑加工时间、集成细胞的剪切敏感性、形状保真度和丝束尺寸。生物墨水由聚合物和细胞的混合物组成，这导致了复杂的流体行为。在本研究中，使用包含藻酸盐、甲基纤维素和琼脂糖（AMA）的生物墨水作为实验模型，将计算出的压力梯度与实验结果进行比较。使用永生化的人骨髓间充质干细胞系和植物细胞（罗勒）进行测试，研究细胞如何影响流动以及打印针内的机械力如何影响细胞活力。两侧的影响都随着细胞（聚集）大小以及更非球形的形状而增加。这项研究有助于对基于挤出的生物打印过程进行系统描述，并介绍了一种通用的工艺设计策略，可转移到其他生物墨水中。
