3D bio-etching of a complex composite-like embryonic tissue.
3D bio-etching of a complex composite-like embryonic tissue.
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DOI：
10.1039/c5lc00530b
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发表时间：
2015-08-21
期刊：
影响因子：
6.1
通讯作者：
Messner WC
中科院分区：
文献类型：
--
作者：
Hazar M;Kim YT;Song J;LeDuc PR;Davidson LA;Messner WC
形态发生涉及一系列复杂的细胞信号、迁移和分化事件，这些事件在胚胎发育过程中随着组织的自组装而协调。细胞的集体运动，如在形态发生过程中发生的运动，通常在2D中被研究，单层培养细胞附着在坚硬的基质上，如玻璃或塑料。在体内，错综复杂的3D微环境和复杂的3D响应在功能组织的形成中起着关键作用。为了研究3D多层组织中的集体细胞运动等过程，我们开发了一种能够产生复杂的3D层流多细胞结构的微流控技术。我们称这种技术为3D组织蚀刻，因为它类似于微电子机械(MEMS)领域中使用的技术，在MEMS领域中，复杂的3D结构是通过减法制造从整体固体中连续移除材料来构建的。我们使用定制设计的微流控系统提供一系列组织蚀刻试剂(洗涤剂、螯合剂、蛋白酶等)。到多层组织的特定区域。这些组织以前是通过显微外科手术从非洲爪趾蛙胚胎中分离出来的。塑造多细胞组织的三维形态和控制三维刺激的能力将对生物工程和医学中的组织工程和再生应用产生重大影响，并在合成高度复杂的三维集成多细胞生物系统方面提供重大改进。为了研究3D多层组织中的集体运动，我们小组专注于开发一种新的微流控技术，能够在多细胞结构中创建复杂的图案。
Morphogenesis involves a complex series of cell signaling, migration and differentiation events that are coordinated as tissues self-assemble during embryonic development. Collective cell movements such as those that occur during morphogenesis have typically been studied in 2D with single layers of cultured cells adhering to rigid substrates such as glass or plastic. In vivo, the intricacies of the 3D microenvironment and complex 3D responses are pivotal in the formation of functional tissues. To study such processes as collective cell movements within 3D multilayered tissues, we developed a microfluidic technique capable of producing complex 3D laminar multicellular structures. We call this technique "3D tissue-etching" because it is analogous to techniques used in the microelectromechanics (MEMS) field where complex 3D structures are built by successively removing material from a monolithic solid through subtractive manufacturing. We use a custom-designed microfluidic control system to deliver a range of tissue etching reagents (detergents, chelators, proteases, etc.) to specific regions of multilayered tissues. These tissues were previously isolated by microsurgical excision from embryos of the African claw-toed frog, Xenopus laevis. The ability to shape the 3D form of multicellular tissues and to control 3D stimulation will have a high impact on tissue engineering and regeneration applications in bioengineering and medicine as well as provide significant improvements in the synthesis of highly complex 3D integrated multicellular biosystems. To investigate the collective movements within 3D multilayered tissues our group has focused on developing a novel microfluidic technique capable of creating complex patterns in multicellular structures.