Abstract
The fabrication of functional microcarriers capable of achieving in vivo-like three-dimensional cell culture is important for many tissue engineering applications. Here, inspired by the structure of Buddha beads, which are generally composed of moveable beads strung on a rope, we present novel cell microcarriers with controllable macropores and heterogeneous microstructures by using a capillary array microfluidic technology. Microfibers with a string of moveable and releasable microcarriers could be achieved by an immediate gelation reaction of sodium alginate spinning and subsequent polymerization of cell-dispersed gelatin methacrylate emulsification. The sizes of the microcarriers and their inner macropores could be well tailored by adjusting the flow rates of the microfluidic phases; this was of great importance in guaranteeing a sufficient supply of nutrients during cell culture. In addition, by infusing multiple cell-dispersed pregel solutions into the capillaries, the microcarriers with spatially heterogeneous cell encapsulations for mimicking physiological structures and functions could also be achieved.
摘要
构建可用于细胞三维培养的多功能微载体在组织工程的应用中至关重要. 本文受佛珠手串中佛珠可以在绳子上自由滑动这一特殊结构的启发, 利用毛细管阵列微流控技术制备了一种具有可控大孔微结构的新型异质细胞微载体, 用于细胞三维培养.仿佛珠微载体的构建首先需要通过海藻酸钠与钙离子的快速凝胶化形成海藻酸钙纤维, 随即在纤维上包覆可聚合的细胞预聚溶液, 通过流体的剪切实现溶液乳化并将其同化聚合, 从而获得串有可以自由滑动的微载体的纤维串.纤维上释放的微载体中间的大孔结构的尺寸高度可控, 这一特点在微载体用于细胞三维培养中具有重要意义, 因为微载体中间的大孔结构能够有效保证载体内部细胞氧气、 营养物质的充分交换, 减少细胞坏死.此外, 通过将多种细胞预聚溶液引入微流控通道中, 还可以获得具有多组分异质结构的细胞微载体, 从而有望实现体内复杂的组织器官结构与功能的模拟.
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Acknowledgements
This work was supported by the National Natural Science Foundation of China (21473029 and 51522302), the NSAF Foundation of China (U1530260), the Natural Science Foundation of Jiangsu (BK20140028), the Program for New Century Excellent Talents in University, the Scientific Research Foundation of Southeast University, and the Scientific Research Foundation of Graduate School of Southeast University.
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Jie Wang received her BSc degree from Southeast University in 2014. She is now a PhD candidate under the supervision of Prof. Yuanjin Zhao at Southeast University. Her research interest is in the fabrication of functional materials based on microfluidics.
Yuanjin Zhao received his PhD degree in 2011 from Southeast University. In 2009–2010, he worked as a research scholar at Prof. David A. Weitz’s group in the School of Engineering and Applied Sciences, Harvard University. Since 2015, he was promoted to be a full professor of Southeast University. His current scientific interests include microfluidic-based materials fabrication, biosensors, and bio-inspired photonic nanomaterials.
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Wang, J., Zou, M., Sun, L. et al. Microfluidic generation of Buddha beads-like microcarriers for cell culture. Sci. China Mater. 60, 857–865 (2017). https://doi.org/10.1007/s40843-017-9081-5
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DOI: https://doi.org/10.1007/s40843-017-9081-5