Magnetic-directed patterning of cell spheroids
Magnetic-directed patterning of cell spheroids
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DOI：
10.1002/jbm.a.34797
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发表时间：
2014-05-01
影响因子：
4.9
通讯作者：
Wen, Xuejun
中科院分区：
文献类型：
--
作者：
Whatley, Benjamin R.;Li, Xiaowei;Wen, Xuejun
我们已经描述了一种方法来制造三维（3D）的细胞为基础的结构，使用功能化的超顺磁性氧化铁纳米粒子（SPION）作为图案化剂，引导组装成3D模式的内皮细胞球体使用的磁力产生的预制磁性模板。SPION首先被内皮细胞摄取，然后通过自制的机器人球体制造机组装成均匀大小的球体。为了引导磁性球体，使用计算机辅助设计制造了一个独特的磁性模板，并从磁性片材上切割下来。然后通过内皮细胞内SPION和磁性模板之间的吸引磁力将球状体引导到预制的磁性模板。内皮细胞球状体在粘附于磁性模板的同时随时间的融合允许形成3D基于细胞的结构。随后去除预制的磁性模板，留下3-D内皮细胞片层，其可以堆叠以制造复杂的3D多细胞组织结构。为了增强细胞相容性，SPION在使用前进行了二氧化硅涂层。在低浓度下，SPION不会对细胞活力、增殖和表型稳定性产生不利影响。光学和共聚焦显微镜显示，内皮细胞球体可以重复创建具有高度均匀性。内皮细胞能够在体外保持活力并维持3D结构。我们已经证明了使用SPION作为图案化剂来指导SPION负载的内皮细胞球状体在预制磁性模板上的附着和自组装以形成3D细胞结构的概念。磁定向技术允许根据期望的磁性图案快速图案化细胞球状体，因此，有望可扩展地制造复杂的3D多细胞组织结构。通过改变细胞类型和预制的磁性图案，这种磁性定向图案化策略可以用于生物打印和多细胞组织移植物制造。(c)2013 Wiley Periodicals，Inc. J Biomed Mater Res Part A：102A：1537-1547，2014.
We have described an approach to fabricate three-dimensional (3D) cell-based structures using functionalized super paramagnetic iron oxide nanoparticles (SPIONs) as patterning agents to guide the assembly of endothelial cell spheroids into 3D patterns using the magnetic forces generated by a prefabricated magnetic template. SPIONs were first uptaken by endothelial cells before they were assembled into uniform-sized spheroids through a home-made robotic spheroid maker. To guide the magnetic spheroids, a unique magnetic template was fabricated using computer-aided design and cut from a magnetic sheet. The spheroids were then guided to the prefabricated magnetic template through the attractive magnetic forces between the SPIONs inside the endothelial cells and the magnetic template. Fusion of endothelial cell spheroids over time while adhered to the magnetic template allowed for the formation of 3D cell-based structures. Subsequent removal of the prefabricated magnetic template left 3-D endothelial cell sheets, which may be stacked to fabricate complicated 3D multicellular tissue structures. To enhance the cytocompatibility, SPIONs were silica-coated before use. At low concentrations, the SPIONs did not adversely affect cell viability, proliferation, and phenotype stability. Light and confocal microscopy showed that endothelial cell spheroids could be reproducibly created with high uniformity. The endothelial cells were able to remain viable and maintain the 3D structure in vitro. We have proved the concept to use SPIONs as a patterning agent to direct the attachment and self assembly of SPION-loaded endothelial cell spheroids on a prefabricated magnetic template for the formation of 3D cell based structures. A magnetic-directed technique allows quick patterning of cell spheroids in accordance with desirable magnetic patterns, therefore, holding promise for scalable fabrication of complicated 3D multicellular tissue structures. By varying the cell types and the prefabricated magnetic patterns, this magnetic-directed patterning strategy may find use in bioprinting and multicellular tissue graft fabrication. (c) 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 102A: 1537-1547, 2014.