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Toward Automated Additive Manufacturing of Living Bio-Tubes Using Ring-Shaped Building Units.
SLAS Technology: Translating Life Sciences Innovation ( IF 2.7 ) Pub Date : 2020-05-26 , DOI: 10.1177/2472630320920896
Kali L Manning 1, 2 , Jacob Feder 1 , Marianne Kanellias 1, 2 , John Murphy 1 , Jeffrey R Morgan 1, 2
Affiliation  

Tissue engineering has been largely confined to academic research institutions with limited success in commercial settings. To help address this issue, more work is needed to develop new automated manufacturing processes for tissue-related technologies. In this article, we describe the automation of the funnel-guide, an additive manufacturing method that uses living tissue rings as building units to form bio-tubes. We developed a method based on 96-well plates and a modified off-the-shelf liquid-handling robot to retrieve, perform real-time quality control, and transfer tissue rings to the funnel-guide. Cells seeded into 96-well plates containing specially designed agarose micromolds self-assembled and formed ring-shaped microtissues that could be retrieved using a liquid-handling robot. We characterized the effects of time, cell type, and mold geometry on the morphology of the ring-shaped microtissues to inform optimal use of the building parts. We programmed and modified an off-the-shelf liquid-handling robot to retrieve ring-shaped microtissues from the 96-well plates, and we fabricated a custom illuminated pipette to visualize each ring-shaped microtissue prior to deposit in the funnel guide. Imaging at the liquid-air interface presented challenges that were overcome by controlling lighting conditions and liquid curvature. Based on these images, we incorporated into our workflow a real-time quality control step based on visual inspection and morphological criteria to assess each ring prior to use. We used this system to fabricate bio-tubes of endothelial cells with luminal alignment.



中文翻译:

使用环形建筑单元实现生物管的自动化增材制造。

组织工程在很大程度上仅限于学术研究机构,在商业环境中取得的成功有限。为了帮助解决这个问题,需要做更多的工作来为组织相关技术开发新的自动化制造工艺。在本文中,我们描述了漏斗导向装置的自动化,这是一种使用活组织环作为构建单元来形成生物管的增材制造方法。我们开发了一种基于 96 孔板和改进的现成液体处理机器人的方法,用于检索、执行实时质量控制并将组织环转移到漏斗导向器。将细胞接种到 96 孔板中,该板含有专门设计的琼脂糖微模,自组装并形成环形微组织,可以使用液体处理机器人进行回收。我们描述了时间、细胞类型、和模具几何形状关于环形微组织的形态,以告知建筑部件的最佳使用。我们对一个现成的液体处理机器人进行了编程和修改,以从 96 孔板中取出环形微组织,并且我们制作了一个定制的发光移液器,以便在将每个环形微组织沉积在漏斗导向器中之前对其进行可视化。液-气界面的成像提出了挑战,这些挑战通过控制光照条件和液体曲率得以克服。基于这些图像,我们将基于视觉检查和形态标准的实时质量控制步骤纳入我们的工作流程,以在使用前评估每个环。我们使用该系统制造具有管腔对齐的内皮细胞生物管。

更新日期:2020-05-26
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