Albrecht Dirk R, Underhill Gregory H, Mendelson Avital, Bhatia Sangeeta N
Harvard-M.I.T. Division of Health Sciences and Technology/Electrical Engineering and Computer Science, Massachusetts Institute of Technology, 77 Massachusetts Ave., E19-502D, Cambridge, MA, USA.
Lab Chip. 2007 Jun;7(6):702-9. doi: 10.1039/b701306j. Epub 2007 Apr 18.
Tissues formed by cells encapsulated in hydrogels have uses in biotechnology, cell-based assays, and tissue engineering. We have previously presented a 3D micropatterning technique that rapidly localizes live cells within hydrogels using dielectrophoretic (DEP) forces, and have demonstrated the ability to modulate tissue function through the control of microscale cell architecture. A limitation of this method is the requirement that a single biomaterial must simultaneously harbor biological properties that support cell survival and function and material properties that permit efficient dielectrophoretic patterning. Here, we resolve this issue by forming multiphase tissues consisting of microscale tissue sub-units in a 'local phase' biomaterial, which, in turn, are organized by DEP forces in a separate, mechanically supportive 'bulk phase' material. We first define the effects of medium conductivity on the speed and quality of DEP cell patterning. As a case study, we then produce multiphase tissues with microscale architecture that combine high local hydrogel conductivity for enhanced survival of sensitive liver progenitor cells with low bulk conductivity required for efficient DEP micropatterning. This approach enables an expanded range of studies examining the influence of 3D cellular architecture on diverse cell types, and in the future may improve the biological function of inhomogeneous tissues assembled from a variety of modular tissue sub-units.
由包裹在水凝胶中的细胞形成的组织在生物技术、基于细胞的分析和组织工程中具有应用价值。我们之前提出了一种三维微图案化技术，该技术利用介电泳（DEP）力将活细胞快速定位在水凝胶中，并展示了通过控制微观尺度的细胞结构来调节组织功能的能力。这种方法的一个局限性在于，单一生物材料必须同时具备支持细胞存活和功能的生物学特性以及允许高效介电泳图案化的材料特性。在此，我们通过在“局部相”生物材料中形成由微观尺度的组织亚单位组成的多相组织来解决这个问题，这些亚单位又通过DEP力在单独的、具有机械支撑作用的“本体相”材料中进行组织。我们首先确定了培养基电导率对DEP细胞图案化速度和质量的影响。作为一个案例研究，我们随后制备了具有微观结构的多相组织，该组织将用于提高敏感肝祖细胞存活率的高局部水凝胶电导率与高效DEP微图案化所需的低本体电导率相结合。这种方法能够开展更广泛的研究，以考察三维细胞结构对多种细胞类型的影响，并且在未来可能会改善由各种模块化组织亚单位组装而成的非均匀组织的生物学功能。
