High-throughput generation of hydrogel microbeads with varying elasticity for cell encapsulation

High-throughput generation of hydrogel microbeads with varying elasticity for cell encapsulation
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DOI:
10.1016/j.biomaterials.2010.10.033
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发表时间:
2011-02-01
期刊:
影响因子:
14
通讯作者:
Kumacheva, Eugenia
Kumacheva, Eugenia
中科院分区:
工程技术1区
文献类型:
--
作者:
Kumachev, Alexander;Greener, Jesse;Kumacheva, Eugenia

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细胞微环境的弹性强烈影响细胞运动、吞噬、生长和分化。目前,细胞行为和基质刚度之间的关系正在研究的平面基板上接种的细胞,然而,在三维(3D)微环境中的细胞可能会经历机械信号,这是不同于一个二维矩阵。我们报告了一种用于高通量生成具有不同弹性的3D微环境的微流体方法,用于细胞命运的研究。具有不同弹性模量的琼脂糖微凝胶的产生通过以下方式实现:(i)将两股琼脂糖溶液流引入微流体液滴发生器中,一股具有高浓度的琼脂糖,另一股具有低浓度的琼脂糖,两股流的相对体积流速比不同,以及(ii)前体液滴的芯片上凝胶化。在37 ° C下,该方法能够使琼脂糖凝胶的剪切弹性模量发生类似于35倍的变化。通过将两个小鼠胚胎干细胞系封装在琼脂糖微凝胶内来证明该方法的应用。这项工作为高通量生成具有不同机械特性的组合微环境用于细胞研究奠定了基础。皇冠版权所有(C)2010由爱思唯尔有限公司出版。保留所有权利。
Elasticity of cellular microenvironments strongly influences cell motility, phagocytosis, growth and differentiation. Currently, the relationship between the cell behaviour and matrix stiffness is being studied for cells seeded on planar substrates, however in three-dimensional (3D) microenvironments cells may experience mechanical signalling that is distinct from that on a two-dimensional matrix. We report a microfluidic approach for high-throughput generation of 3D microenvironments with different elasticity for studies of cell fate. The generation of agarose microgels with different elastic moduli was achieved by (i) introducing into a microfluidic droplet generator two streams of agarose solutions, one with a high concentration of agarose and the other one with a low concentration of agarose, at varying relative volumetric flow rate ratios of the two streams, and (ii) on-chip gelation of the precursor droplets. At 37 degrees C, the method enabled a similar to 35-fold variation of the shear elastic modulus of the agarose gels. The application of the method was demonstrated by encapsulating two mouse embryonic stem cell lines within the agarose microgels. This work establishes a foundation for the high-throughput generation of combinatorial microenvironments with different mechanical properties for cell studies. Crown Copyright (C) 2010 Published by Elsevier Ltd. All rights reserved.