Effects of transglutaminase cross-linking process on printability of gelatin microgel-gelatin solution composite bioink
Effects of transglutaminase cross-linking process on printability of gelatin microgel-gelatin solution composite bioink
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DOI：
10.1088/1758-5090/ac3d75
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发表时间：
2021-11
期刊：
影响因子：
9
通讯作者：
Kaidong Song;B. Ren;Yingnan Zhai;Wenxuan Chai;Yong Huang
中科院分区：
文献类型：
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作者：
Kaidong Song;B. Ren;Yingnan Zhai;Wenxuan Chai;Yong Huang
三维 (3D) 生物打印已成为各种组织工程应用的强大工程方法，特别是用于开发具有独特机械和/或生物特性的 3D 细胞结构。对于堵塞的明胶微凝胶-明胶溶液复合生物墨水，由微凝胶的离散相（酶促凝胶明胶微凝胶）和含有转谷氨酰胺酶（TG）的可交联的连续明胶前体溶液相组成，由于TG酶诱导的交联过程，其流变特性和可印刷性逐渐变化。本研究的目的是建立基于明胶微凝胶-明胶溶液的可交联复合生物墨水的可印刷性与TG浓度和交联时间之间的直接映射。由于复合生物墨水中包含TG，生物墨水一旦制备就开始交联，并且通常在打印过程之前制备。在此，生物墨水的可打印性根据三个指标进行评估：可注射性、特征可成形性和过程诱导的细胞损伤。在这项研究中，首先使用一级交联动力学模型系统地研究和预测了交联过程中不同TG浓度和时间下的储能模量和粘度等流变特性。储能模量和粘度已令人满意地建模为 TG 浓度和时间的指数函数，并具有实验校准的交联动力学速率常数。此外，可注射性、特征可成形性和过程引起的细胞损伤已通过储能模量、粘度和/或过程引起的剪切应力成功地与TG浓度和交联时间相关联。通过结合良好的可注射性、良好的特征成形性和令人满意的细胞活力区域，在打印基于小鼠成纤维细胞的2%明胶B微凝胶-3%明胶B溶液复合生物墨水时，建立了良好的可打印区域（对于具有1.00、2.00和4.00% w/v TG的复合生物墨水分别为1.65、0.61和0.31小时）。这种适印区方法可以扩展到使用其他可交联生物墨水进行生物打印应用。
Three-dimensional (3D) bioprinting has emerged as a powerful engineering approach for various tissue engineering applications, particularly for the development of 3D cellular structures with unique mechanical and/or biological properties. For the jammed gelatin microgel-gelatin solution composite bioink, comprising a discrete phase of microgels (enzymatically gelled gelatin microgels) and a cross-linkable continuous gelatin precursor solution-based phase containing transglutaminase (TG), its rheological properties and printability change gradually due to the TG enzyme-induced cross-linking process. The objective of this study is to establish a direct mapping between the printability of the gelatin microgel-gelatin solution based cross-linkable composite bioink and the TG concentration and cross-linking time, respectively. Due to the inclusion of TG in the composite bioink, the bioink starts cross-linking once prepared and is usually prepared right before a printing process. Herein, the bioink printability is evaluated based on the three metrics: injectability, feature formability, and process-induced cell injury. In this study, the rheological properties such as the storage modulus and viscosity have been first systematically investigated and predicted at different TG concentrations and times during the cross-linking process using the first-order cross-linking kinetics model. The storage modulus and viscosity have been satisfactorily modeled as exponential functions of the TG concentration and time with an experimentally calibrated cross-linking kinetic rate constant. Furthermore, the injectability, feature formability, and process-induced cell injury have been successfully correlated to the TG concentration and cross-linking time via the storage modulus, viscosity, and/or process-induced shear stress. By combing the good injectability, good feature formability, and satisfactory cell viability zones, a good printability zone (1.65, 0.61, and 0.31 h for the composite bioinks with 1.00, 2.00, and 4.00% w/v TG, respectively) has been established during the printing of mouse fibroblast-based 2% gelatin B microgel-3% gelatin B solution composite bioink. This printability zone approach can be extended to the use of other cross-linkable bioinks for bioprinting applications.