Cell Sheet‐Based Tissue Engineering for Organizing Anisotropic Tissue Constructs Produced Using Microfabricated Thermoresponsive Substrates
Cell Sheet‐Based Tissue Engineering for Organizing Anisotropic Tissue Constructs Produced Using Microfabricated Thermoresponsive Substrates
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DOI：
10.1002/adhm.201500194
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发表时间：
2015-06
影响因子：
10
通讯作者：
Hironobu Takahashi;T. Okano
中科院分区：
文献类型：
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作者：
Hironobu Takahashi;T. Okano
在一些天然组织中，适当的微观结构，包括细胞/细胞外基质的取向，提供了特定的机械和生物学功能。例如，骨骼肌是由负责机械功能的定向肌纤维组成的。原生动脉和心肌组织是通过排列细胞的片状组织堆叠而成的。因此，为了构建任何一种复杂的组织，细胞的微观结构，如肌管、平滑肌细胞和心肌细胞，也需要像在身体的天然组织中一样进行三维组织。基于细胞片的组织工程允许通过一层一层的构建技术生产无支架的工程组织。最近，利用微加工的热敏衬底，排列的细胞被收获为单个连续的细胞片。细胞片作为各向异性组织单元，构建具有适当各向异性的三维组织结构。这种基于细胞片的技术是直接的，并且具有设计各种复杂组织的潜力。此外，由于无支架细胞密集的环境，这些细胞片结构的物理和生物细胞间相互作用表现出独特的细胞行为。这些优势将为未来组织工程所需的组织工程提供重要线索，使组织良好的组织能够模仿天然组织的结构和功能。
In some native tissues, appropriate microstructures, including orientation of the cell/extracellular matrix, provide specific mechanical and biological functions. For example, skeletal muscle is made of oriented myofibers that is responsible for the mechanical function. Native artery and myocardial tissues are organized three‐dimensionally by stacking sheet‐like tissues of aligned cells. Therefore, to construct any kind of complex tissue, the microstructures of cells such as myotubes, smooth muscle cells, and cardiomyocytes also need to be organized three‐dimensionally just as in the native tissues of the body. Cell sheet‐based tissue engineering allows the production of scaffold‐free engineered tissues through a layer‐by‐layer construction technique. Recently, using microfabricated thermoresponsive substrates, aligned cells are being harvested as single continuous cell sheets. The cell sheets act as anisotropic tissue units to build three‐dimensional tissue constructs with the appropriate anisotropy. This cell sheet‐based technology is straightforward and has the potential to engineer a wide variety of complex tissues. In addition, due to the scaffold‐free cell‐dense environment, the physical and biological cell–cell interactions of these cell sheet constructs exhibit unique cell behaviors. These advantages will provide important clues to enable the production of well‐organized tissues that closely mimic the structure and function of native tissues, required for the future of tissue engineering.