Strauß Svenja, Schroth Bianca, Hubbuch Jürgen
Karlsruhe Institute of Technology, Institute of Functional Interfaces, Karlsruhe, Germany.
Institute of Engineering in Life Sciences, Section IV: Molecular Separation Engineering, Karlsruhe Institute of Technology, Karlsruhe, Germany.
Front Bioeng Biotechnol. 2022 Mar 3;10:831350. doi: 10.3389/fbioe.2022.831350. eCollection 2022.
Bioprinting is increasingly regarded as a suitable additive manufacturing method in biopharmaceutical process development and formulation. In order to manage the leap from research to industrial application, higher levels of reproducibility and a standardized bioprinting process are prerequisites. This said, the concept of process analytical technologies, standard in the biopharmaceutical industry, is still at its very early steps. To date most extrusion-based printing processes are controlled over penumatic pressure and thus not adaptive to environmental or system related changes over several experimental runs. A constant set pressure applied over a number of runs, might lead to variations in flow rate and thus to unreliable printed constructs. With this in mind, the simple question arises whether a printing process based on a set flow rate could improve reproduciblity and transfer to different printing systems. The control and monitoring of flow rate aim to introduce the concept of PAT in the field of bioprinting. This study investigates the effect of different processing modes (set pressure vs. set flow rate) on printing reproducibility occurring during an extrusion-based printing process consisting of 6 experimental runs consisting of 3 printed samples each. Additionally, the influence of different filling levels of the ink containing cartridge during a printing process was determined. Different solutions based on a varying amount of alginate polymer and Kolliphor hydrogels in varying concentrations showed the need for individual setting of printing parameter. To investigate parameter transferability among different devices two different printers were used and the flow was monitored using a flow sensor attached to the printing unit. It could be demonstrated that a set flow rate controlled printing process improved accuracy and the filling level also affects the accuracy of printing, the magnitude of this effects varies as the cartridge level declined. The transferability between printed devices was eased by setting the printing parameters according to a set flow rate of each bioink disregarding the value of the set pressure. Finally, by a bioprinting porcess control based on a set flow rate, the coefficient of variance for printed objects could be reduced from 0.2 to 0.02 for 10% (w/v) alginate polymer solutions.
生物打印越来越被视为生物制药工艺开发和制剂中的一种合适的增材制造方法。为了实现从研究到工业应用的跨越，更高水平的可重复性和标准化的生物打印工艺是先决条件。话虽如此，生物制药行业的标准工艺分析技术概念仍处于非常早期的阶段。迄今为止，大多数基于挤压的打印工艺是通过气动压力控制的，因此在多次实验运行中无法适应环境或系统相关的变化。在多次运行中施加恒定的设定压力可能会导致流速变化，从而导致打印结构不可靠。考虑到这一点，就会产生一个简单的问题，即基于设定流速的打印工艺是否可以提高可重复性并转移到不同的打印系统。流速的控制和监测旨在在生物打印领域引入过程分析技术的概念。本研究调查了不同处理模式（设定压力与设定流速）对基于挤压的打印过程中打印可重复性的影响，该过程由6次实验运行组成，每次运行包含3个打印样品。此外，还确定了打印过程中含墨墨盒不同填充水平的影响。基于不同浓度的不同量藻酸盐聚合物和聚氧乙烯蓖麻油水凝胶的不同溶液表明需要单独设置打印参数。为了研究不同设备之间的参数可转移性，使用了两台不同的打印机，并使用连接到打印单元的流量传感器监测流量。可以证明，设定流速控制的打印过程提高了精度，填充水平也会影响打印精度，随着墨盒液位下降，这种影响的程度会有所不同。通过根据每种生物墨水的设定流速设置打印参数，而不考虑设定压力的值，可以简化打印设备之间的可转移性。最后，通过基于设定流速的生物打印过程控制，对于10%（w/v）藻酸盐聚合物溶液，打印物体的变异系数可以从0.2降低到0.02。
