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High-Resolution Patterned Cellular Constructs by Droplet-Based 3D Printing

机译:基于液滴的3D打印的高分辨率图案化细胞结构

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摘要

Bioprinting is an emerging technique for the fabrication of living tissues that allows cells to be arranged in predetermined three-dimensional (3D) architectures. However, to date, there are limited examples of bioprinted constructs containing multiple cell types patterned at high-resolution. Here we present a low-cost process that employs 3D printing of aqueous droplets containing mammalian cells to produce robust, patterned constructs in oil, which were reproducibly transferred to culture medium. Human embryonic kidney (HEK) cells and ovine mesenchymal stem cells (oMSCs) were printed at tissue-relevant densities (107 cells mL−1) and a high droplet resolution of 1 nL. High-resolution 3D geometries were printed with features of ≤200 μm; these included an arborised cell junction, a diagonal-plane junction and an osteochondral interface. The printed cells showed high viability (90% on average) and HEK cells within the printed structures were shown to proliferate under culture conditions. Significantly, a five-week tissue engineering study demonstrated that printed oMSCs could be differentiated down the chondrogenic lineage to generate cartilage-like structures containing type II collagen.
机译:生物打印是一种用于制造活体组织的新兴技术,该技术允许将细胞排列在预定的三维(3D)结构中。然而,迄今为止,包含以高分辨率模式化的多种细胞类型的生物印刷构建体的例子有限。在这里,我们提出了一种低成本流程,该流程采用3D打印包含哺乳动物细胞的水滴的方法,以在油中生成坚固的,有图案的构建体,然后可复制地转移到培养基中。以与组织相关的密度(10 7 细胞mL -1 )和高液滴分离度打印人胚肾(HEK)细胞和绵羊间充质干细胞(oMSCs)。 1升高分辨率3D几何图形的特征​​≤200μm;其中包括一个乔木化的细胞连接,一个对角平面连接和一个骨软骨界面。印刷的细胞显示出高生存力(平均90%),并且印刷结构内的HEK细胞显示在培养条件下增殖。重要的是,一项为期五周的组织工程研究表明,打印的oMSC可以沿软骨生成谱系分化,从而生成包含II型胶原的软骨样结构。

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