Guiding Cell Network Assembly using Shape-Morphing Hydrogels.

Guiding Cell Network Assembly using Shape-Morphing Hydrogels.
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DOI:
10.1002/adma.202002195
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发表时间:
2020-08
期刊:
Advanced materials (Deerfield Beach, Fla.)
影响因子:
--
通讯作者:
Hughes AJ
Hughes AJ
中科院分区:
其他
文献类型:
--
作者:
Viola JM;Porter CM;Gupta A;Alibekova M;Prahl LS;Hughes AJ

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细胞与细胞外基质(ECM)之间的力和相对运动对于组织在发育过程中的自组织至关重要。然而,在工程方法中可以控制这些动力学的空间范围是有限的,阻碍了构建大的结构成熟组织的进展。在此,描述了被称为“kinomorphs”的形状变形材料,其合理地控制多细胞网络的形状和尺寸。Kinomorphs是ECM片,其形状,大小和密度取决于其中细胞收缩的模式。研究表明,这些变化可以同时操纵许多空间位置的上皮细胞的结构形成行为。Kinomorphs是使用一种新的细胞外基质技术构建的,将单个细胞图案化为比先前描述的大10倍的ECM片。这些图案被设计成部分模仿胚胎肾上皮网络的分支几何形状。折纸启发的模拟,然后用来预测的Kinomorph形状的变化。最后,Kinomorph动力学显示提供了一个厘米级的程序,该程序设置了特定的空间位置,在该空间位置中,通过细胞聚结和结构成熟形成直径为50 μ m的上皮小管。这些Kinomorphs可以通过扩展新兴模型系统(如类器官)中细胞自组织的空间范围来显着推进器官规模的组织构建。
Forces and relative movement between cells and extracellular matrix (ECM) are crucial to the self-organization of tissues during development. However, the spatial range over which these dynamics can be controlled in engineering approaches is limited, impeding progress toward the construction of large, structurally mature tissues. Herein, shape-morphing materials called “kinomorphs” that rationally control the shape and size of multicellular networks are described. Kinomorphs are sheets of ECM that change their shape, size, and density depending on patterns of cell contractility within them. It is shown that these changes can manipulate structure-forming behaviors of epithelial cells in many spatial locations at once. Kinomorphs are built using a new photolithographic technology to pattern single cells into ECM sheets that are >10× larger than previously described. These patterns are designed to partially mimic the branch geometry of the embryonic kidney epithelial network. Origami-inspired simulations are then used to predict changes in kinomorph shapes. Last, kinomorph dynamics are shown to provide a centimeter-scale program that sets specific spatial locations in which ≈50 μm-diameter epithelial tubules form by cell coalescence and structural maturation. The kinomorphs may significantly advance organ-scale tissue construction by extending the spatial range of cell self-organization in emerging model systems such as organoids.
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