Tissue engineering by self-assembly of cells printed into topologically defined structures

Tissue engineering by self-assembly of cells printed into topologically defined structures
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DOI:
10.1089/tea.2007.0173
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发表时间:
2008-03-01
影响因子:
4.1
通讯作者:
Forgacs, Gabor
Forgacs, Gabor
中科院分区:
医学3区
文献类型:
--
作者:
Jakab, Karoly;Norotte, Cyrille;Forgacs, Gabor

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了解生物自组装的原理对于开发建立活组织和器官的有效策略是必不可少的。我们利用细胞和组织的自组织能力来构建指定形状的功能生命结构。在我们的技术中,多细胞球体(生物墨水颗粒)通过使用三维递送设备(生物打印机)被放置到生物兼容环境(生物纸)中。我们的方法模拟了早期的形态发生,并基于这样一种认识,即通过自组装对发育模式的遗传控制涉及到物理机制。三维组织结构是通过生物墨水颗粒的打印后融合形成的,类似于胚胎中的早期结构形成过程,该过程利用了由活动细胞和粘连细胞组成的组织的明显的液体行为。我们模拟了生物墨水颗粒融合的自组装过程,并利用这一新技术打印了各种形状的扩展细胞结构。在由胚胎心脏和内皮细胞构建的心脏结构上进行了功能测试。打印后生物墨水颗粒的自组装导致固体组织块同步跳动,显示出早期血管形成的迹象,内皮细胞组织成血管状管道。
Understanding the principles of biological self-assembly is indispensable for developing efficient strategies to build living tissues and organs. We exploit the self-organizing capacity of cells and tissues to construct functional living structures of prescribed shape. In our technology, multicellular spheroids (bio-ink particles) are placed into biocompatible environment (bio-paper) by the use of a three-dimensional delivery device (bio-printer). Our approach mimics early morphogenesis and is based on the realization that the genetic control of developmental patterning through self-assembly involves physical mechanisms. Three-dimensional tissue structures are formed through the postprinting fusion of the bio- ink particles, in analogy with early structure-forming processes in the embryo that utilize the apparent liquid-like behavior of tissues composed of motile and adhesive cells. We modeled the process of self-assembly by fusion of bio-ink particles, and employed this novel technology to print extended cellular structures of various shapes. Functionality was tested on cardiac constructs built from embryonic cardiac and endothelial cells. The postprinting self-assembly of bio- ink particles resulted in synchronously beating solid tissue blocks, showing signs of early vascularization, with the endothelial cells organized into vessel-like conduits.