Directed self-assembly of large scaffold-free multi-cellular honeycomb structures.

Directed self-assembly of large scaffold-free multi-cellular honeycomb structures.
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DOI:
10.1088/1758-5082/3/3/034110
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发表时间:
2011-09
期刊:
影响因子:
9
通讯作者:
Morgan JR
Morgan JR
中科院分区:
工程技术1区
文献类型:
--
作者:
Tejavibulya N;Youssef J;Bao B;Ferruccio TM;Morgan JR

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生物制造领域的一个重大挑战是快速构建大型三维(3D)活体组织和器官。多细胞球体已被用作构建块。在本文中,我们利用定向自组装技术创建了大型多细胞蜂窝结构单元,从而在微模具的形状和障碍物的背景下,细胞与细胞之间的粘附驱动了 3D 结构的形成。使用计算机辅助设计、快速原型制作和复制成型来制造蜂窝状微型模具。由这些微模具浇铸的非粘性水凝胶在细胞培养基中平衡并接种两种类型的哺乳动物细胞。细胞沉入蜂窝凹部,无法附着在非粘附性水凝胶上,因此细胞与细胞之间的粘附驱动了大型多细胞蜂窝在 24 小时内的自组装。蜂窝及其细胞发生了明显的形态变化,表明存在显着的细胞介导的张力。与球体不同,球体的尺寸受到维持细胞活力所需的临界扩散距离的限制,而蜂窝体的总体尺寸不受限制。蜂窝建筑单元的快速生产,具有多个高密度细胞环和开放的内腔空间,为生物制造策略提供了有趣的新可能性。
A significant challenge to the field of biofabrication is the rapid construction of large three dimensional (3D) living tissues and organs. Multi-cellular spheroids have been used as building blocks. In this paper, we create large multi-cellular honeycomb building blocks using directed self-assembly, whereby cell-to-cell adhesion, in the context of the shape and obstacles of a micromold, drives the formation of a 3D structure. Computer aided design, rapid prototyping and replica molding were used to fabricate honeycomb-shaped micro-molds. Nonadhesive hydrogels cast from these micro-molds were equilibrated in cell culture medium and seeded with two types of mammalian cells. The cells settled into the honeycomb recess, were unable to attach to the nonadhesive hydrogel and so cell-to-cell adhesion drove the self-assembly of a large multicellular honeycomb within 24 hours. Distinct morphological changes occurred to the honeycomb and its cells indicating the presence of significant cell-mediated tension. Unlike the spheroid, whose size is constrained by a critical diffusion distance needed to maintain cell viability, the overall size of the honeycomb is not limited. The rapid production of the honeycomb building unit, with its multiple rings of high density cells and open lumen spaces, offers interesting new possibilities for biofabrication strategies.
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