Hydrogel-based biomimetic environment for in vitro modulation of branching morphogenesis

Hydrogel-based biomimetic environment for in vitro modulation of branching morphogenesis
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DOI:
10.1016/j.biomaterials.2011.05.072
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发表时间:
2011-10-01
期刊:
影响因子:
14
通讯作者:
Imazato, Satoshi
Imazato, Satoshi
中科院分区:
工程技术1区
文献类型:
--
作者:
Miyajima, Hiroyuki;Matsumoto, Takuya;Imazato, Satoshi

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在组织发育和生长过程中,细胞微环境的力学特性发生了巨大的变化。越来越多的证据表明,物理微环境和机械应力直接影响发育组织中的细胞命运。然而,这些物理线索如何影响组织形态发生仍然是一个主要的未知数。我们在此解释了细胞和组织微环境的物理特性,通过水凝胶仿生再现,指导发育中的下颌下腺(SMG)组织形态发生。特别是,较软的凝胶增强了SMG的芽扩展和裂缝形成,而较硬的凝胶则减弱了它们。SMG组织的这些形态变化是由可溶性因子(FGF7/10)诱导的,由组织变形产生的细胞牵引力调节。我们的研究结果表明,细胞感知其周围环境的机制,并改变其自组织和随后的组织形态发生的性质。此外,物理设计的水凝胶材料是一种有价值的工具,用于产生仿生微环境,以探索物理线索如何影响组织形态发生,并调节组织形态发生以进行体外组织合成。(C) 2011 Elsevier Ltd.版权所有。
The mechanical properties of the cellular microenvironment dramatically alter during tissue development and growth. Growing evidence suggests that physical microenvironments and mechanical stresses direct cell fate in developing tissue. However, how these physical cues affect the tissue morphogenesis remains a major unknown. We explain here that the physical properties of the cell and tissue microenvironment, biomimetically reproduced by using hydrogel, guide the tissue morphogenesis in the developmental submandibular gland (SMG). In particular, the softer gel enhances the bud expansion and cleft formation of SMG, whereas the stiffer gel attenuates them. These morphological changes in SMG tissue are led by soluble factors (FGF7/10) induction regulated by cell traction force derived from the tissue deformation. Our findings suggest that cells sense the mechanics of their surrounding environment and alter their properties for self-organization and the following tissue morphogenesis. Also, physically designed hydrogel material is a valuable tool for producing the biomimetic microenvironment to explore how physical cues affect tissue morphogenesis and to modulate tissue morphogenesis for in vitro tissue synthesis. (C) 2011 Elsevier Ltd. All rights reserved.