The influence of printing parameters on cell survival rate and printability in microextrusion-based 3D cell printing technology
The influence of printing parameters on cell survival rate and printability in microextrusion-based 3D cell printing technology
复制标题
基于微挤压的3D细胞打印技术中打印参数对细胞存活率和打印适性的影响
DOI：
10.1088/1758-5090/7/4/045002
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发表时间：
2015-12-01
期刊：
影响因子：
9
通讯作者：
Yao, Rui
中科院分区：
文献类型：
--
作者：
Zhao, Yu;Li, Yang;Yao, Rui
三维（3D）细胞打印技术为组织工程、药物测试和筛选应用提供了一种通用的方法来制造细胞负载的组织样结构和体外组织/病理模型。然而，如何在打印出高粘弹性的生物油墨后，在实现长期稳定结构的同时，保持较高的细胞存活率，仍然是一个挑战。在本研究中，我们系统地研究了3D细胞打印参数，即生物墨水的组成和浓度、保温温度和保温时间对微挤压3D细胞打印技术的可打印性和细胞存活率的影响。利用流变学测量来表征明胶基生物墨水的粘弹性。结果表明，在胶凝温度以下，随着生物胶浓度的增加、保温时间的延长和保温温度的降低，生物胶的粘弹性增加。当增加明胶基生物墨水的粘弹性时，观察到3D细胞打印过程后细胞存活率的下降。然而，不同的工艺参数组合会导致相似的流变特性，从而在3D生物打印过程中显示出相似的细胞存活率。另一方面，生物油墨的粘弹性也应达到一定程度，以保证良好的印刷适性和形状保真度。最后，我们提出了一种具有高细胞存活率和良好打印性的温敏明胶基水凝胶生物墨水的3D生物打印方案。该研究可为生物制造研究人员快速调整生物3D打印工艺参数提供参考，并可作为设计新型生物墨水的参考模板。
Three-dimensional (3D) cell printing technology has provided a versatile methodology to fabricate cell-laden tissue-like constructs and in vitro tissue/pathological models for tissue engineering, drug testing and screening applications. However, it still remains a challenge to print bioinks with high viscoelasticity to achieve long-term stable structure and maintain high cell survival rate after printing at the same time. In this study, we systematically investigated the influence of 3D cell printing parameters, i.e. composition and concentration of bioink, holding temperature and holding time, on the printability and cell survival rate in microextrusion-based 3D cell printing technology. Rheological measurements were utilized to characterize the viscoelasticity of gelatin-based bioinks. Results demonstrated that the bioink viscoelasticity was increased when increasing the bioink concentration, increasing holding time and decreasing holding temperature below gelation temperature. The decline of cell survival rate after 3D cell printing process was observed when increasing the viscoelasticity of the gelatin-based bioinks. However, different process parameter combinations would result in the similar rheological characteristics and thus showed similar cell survival rate after 3D bioprinting process. On the other hand, bioink viscoelasticity should also reach a certain point to ensure good printability and shape fidelity. At last, we proposed a protocol for 3D bioprinting of temperature-sensitive gelatin-based hydrogel bioinks with both high cell survival rate and good printability. This research would be useful for biofabrication researchers to adjust the 3D bioprinting process parameters quickly and as a referable template for designing new bioinks.