Self-Assembly and Tissue Fusion of Toroid-Shaped Minimal Building Units

Self-Assembly and Tissue Fusion of Toroid-Shaped Minimal Building Units
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DOI:
10.1089/ten.tea.2009.0607
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发表时间:
2010-06-01
影响因子:
4.1
通讯作者:
Morgan, Jeffrey R.
Morgan, Jeffrey R.
中科院分区:
医学3区
文献类型:
--
作者:
Livoti, Christine M.;Morgan, Jeffrey R.

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组织工程的一个重大挑战是构建尺寸不受扩散限制的组织。我们正在研究使用无支架管腔包含环形微组织作为最小的建筑单位。将单分散的大鼠肝细胞系H35细胞接种在微模琼脂糖上,48 h内形成自组装的多细胞环。环和管腔直径容易通过微模具设计控制,环厚度通过接种密度控制。当采集时,环是稳定的,但随着时间的推移发生了可预测的变化,管腔变窄。当接触时,这些构建单元在x-y平面中融合,形成双腔结构,以及在z平面中融合,形成管状结构,其在72 h内完成。通过多个环形的多维融合来组装大的多腔结构。环形沉降不是完全随机的,大多数环形平放,其内腔沿着z轴定向。快速生产具有受控尺寸和管腔尺寸的环形构建单元,其经历可预测的变化并且可以融合以形成更大的结构,这是向具有高细胞密度的组织工程大多孔三维组织更近的一步。
A significant challenge of tissue engineering is to build tissues whose size is not limited by diffusion. We are investigating the use of scaffold-free lumen containing toroid-shaped microtissues as minimal building units. Monodispersed H35 cells, a rat hepatocyte cell line, were seeded onto micromolded agarose, forming self-assembled multicellular toroids within 48 h. Toroid and lumen diameter were easily controlled by micromold design, and toroid thickness was controlled by seeding density. When harvested, toroids were stable, but underwent predictable changes over time with their lumens narrowing. When brought into contact, these building units fused in the x-y plane, forming a double-lumen structure, as well as the z plane, forming a tubular structure, which completed within 72 h. Large, multi-luminal structures were assembled by multidimensional fusion of many toroids. Toroid settling was not entirely random, with most toroids lying flat with their lumens oriented along the z axis. The rapid production of toroid building units of controlled dimension and lumen size that undergo predictable changes and that can be fused to form larger structures is a step closer to tissue engineering large porous three-dimensional tissues with high cell density.