Bio-Pick, Place, and Perfuse: A New Instrument for Three-Dimensional Tissue Engineering

Bio-Pick, Place, and Perfuse: A New Instrument for Three-Dimensional Tissue Engineering
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DOI:
10.1089/ten.tec.2014.0439
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发表时间:
2015-07-01
影响因子:
3
通讯作者:
Morgan, Jeffrey R.
Morgan, Jeffrey R.
中科院分区:
医学4区
文献类型:
--
作者:
Blakely, Andrew M.;Manning, Kali L.;Morgan, Jeffrey R.

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组织工程的一个巨大挑战是制造具有高密度活细胞的大型结构。通过调整用于高速电子组装的拾取和放置机器的原理,我们开发了一种创新仪器,Bio-Pick,Place,and Perfuse(Bio-P3),它拾取大型复杂的多细胞构建部件,将它们运送到构建区域,并在灌注部件的同时将部件精确放置在所需位置。这些组装的部分随后融合以形成更大的连续组织构建体。通过将细胞接种到非粘附性微模具中形成多细胞微组织,其中细胞自组装成球形、环形和蜂窝形状的无支架部分。从模具中取出后,将部件夹持、运输(使用x、y、z控制器),并使用Bio-P3释放,对细胞活力或部件结构几乎没有影响。将多达16个环形体堆叠在170 μ m直径的柱上,其中它们在48小时的过程中融合以形成单个组织。较大的蜂窝部件也被夹持并堆叠到构建头上,该构建头与夹持头一样,在组装期间提供流体抽吸以保持和灌注部件。无支架建筑部件有助于解决大型组织生物制造的几个工程和生物挑战,本文中描述的Bio-P3是一种新型仪器,用于固体器官制造的活建筑部件的受控夹持,放置,堆叠和灌注。
A grand challenge of tissue engineering is the fabrication of large constructs with a high density of living cells. By adapting the principles of pick-and-place machines used in the high-speed assembly of electronics, we have developed an innovative instrument, the Bio-Pick, Place, and Perfuse (Bio-P3), which picks up large complex multicellular building parts, transports them to a build area, and precisely places the parts at desired locations while perfusing the parts. These assembled parts subsequently fuse to form a larger contiguous tissue construct. Multicellular microtissues were formed by seeding cells into nonadhesive micro-molds, wherein cells self-assembled scaffold-free parts in the shape of spheroids, toroids, and honeycombs. After removal from the molds, the parts were gripped, transported (using an x, y, z controller), and released using the Bio-P3 with little to no effect on cell viability or part structure. As many as 16 toroids were stacked over a 170 mu m diameter post where they fused over the course of 48 h to form a single tissue. Larger honeycomb parts were also gripped and stacked onto a build head that, like the gripper head, provided fluid suction to hold and perfuse the parts during assembly. Scaffold-free building parts help to address several of the engineering and biological challenges to large tissue biofabrication, and the Bio-P3 described in this article is a novel instrument for the controlled gripping, placing, stacking, and perfusing of living building parts for solid organ fabrication.