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评估基于挤出式生物打印的生物墨水可印刷性的提案和评估控制生物打印性的流变学性质的评价。

Proposal to assess printability of bioinks for extrusion-based bioprinting and evaluation of rheological properties governing bioprintability.

机构信息

Department for Functional Materials in Medicine and Dentistry and Bavarian Polymer Institute, Julius-Maximilians-Universität Würzburg, Germany. Institute of Health and Biomedical Innovation, Queensland University of Technology (QUT), Brisbane, Australia.

出版信息

Biofabrication. 2017 Nov 14;9(4):044107. doi: 10.1088/1758-5090/aa8dd8.

DOI:10.1088/1758-5090/aa8dd8
PMID:28930091
Abstract

The development and formulation of printable inks for extrusion-based 3D bioprinting has been a major challenge in the field of biofabrication. Inks, often polymer solutions with the addition of crosslinking to form hydrogels, must not only display adequate mechanical properties for the chosen application but also show high biocompatibility as well as printability. Here we describe a reproducible two-step method for the assessment of the printability of inks for bioprinting, focussing firstly on screening ink formulations to assess fibre formation and the ability to form 3D constructs before presenting a method for the rheological evaluation of inks to characterise the yield point, shear thinning and recovery behaviour. In conjunction, a mathematical model was formulated to provide a theoretical understanding of the pressure-driven, shear thinning extrusion of inks through needles in a bioprinter. The assessment methods were trialled with a commercially available crème, poloxamer 407, alginate-based inks and an alginate-gelatine composite material. Yield stress was investigated by applying a stress ramp to a number of inks, which demonstrated the necessity of high yield for printable materials. The shear thinning behaviour of the inks was then characterised by quantifying the degree of shear thinning and using the mathematical model to predict the window of printer operating parameters in which the materials could be printed. Furthermore, the model predicted high shear conditions and high residence times for cells at the walls of the needle and effects on cytocompatibility at different printing conditions. Finally, the ability of the materials to recover to their original viscosity after extrusion was examined using rotational recovery rheological measurements. Taken together, these assessment techniques revealed significant insights into the requirements for printable inks and shear conditions present during the extrusion process and allow the rapid and reproducible characterisation of a wide variety of inks for bioprinting.

摘要

用于挤出式 3D 生物打印的可打印墨水的开发和配方一直是生物制造领域的主要挑战。墨水通常是聚合物溶液,添加交联剂以形成水凝胶,不仅必须具有足够的机械性能,而且还必须具有高生物相容性和可打印性。在这里,我们描述了一种可重复的两步法,用于评估生物打印用墨水的可打印性,首先侧重于筛选墨水配方,以评估纤维形成和形成 3D 结构的能力,然后介绍一种用于评估墨水的流变学特性的方法,以表征屈服点、剪切变稀和恢复行为。同时,还提出了一个数学模型,以提供对压力驱动的、通过生物打印机中的针头进行剪切变稀挤出的墨水的理论理解。评估方法用一种市售的乳膏、泊洛沙姆 407、基于海藻酸盐的墨水和海藻酸盐-明胶复合材料进行了测试。通过对几种墨水施加应力斜坡来研究屈服应力,这证明了可打印材料需要高屈服应力。然后通过量化剪切变稀程度并使用数学模型来预测材料可打印的打印机操作参数窗口来表征墨水的剪切变稀行为。此外,该模型预测了高剪切条件和细胞在针壁处的高停留时间以及不同打印条件对细胞相容性的影响。最后,使用旋转恢复流变测量来检查材料在挤出后恢复到原始粘度的能力。总之,这些评估技术揭示了对可打印墨水的要求以及挤出过程中存在的剪切条件的重要见解,并允许快速、可重复地对各种用于生物打印的墨水进行特性描述。

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