Perfused Organ Cell‐Dense Macrotissues Assembled from Prefabricated Living Microtissues
Perfused Organ Cell‐Dense Macrotissues Assembled from Prefabricated Living Microtissues
复制标题
由预制活体微组织组装而成的灌注器官细胞致密大组织
作者：
Blanche C. Ip;F. Cui;Benjamin T Wilks;John Murphy;A. Tripathi;J. Morgan
工程组织通常达不到生理细胞密度和大小，导致功能性能有限。大组织的活力受到扩散驱动的营养交换不足的限制。缺乏形成大的活组织的方法，并且受到扩散驱动的营养交换的限制。在这里，报告了使用Bio‐Pick，Place，and Perfuse（Bio‐P3），这是一种集成的生物组织-生物反应器平台，可以半自动和快速地组装具有1亿个细胞的生理细胞密集的大组织，同时进行主动灌注。Bio‐P3在可灌注构建平台上夹持、对齐和堆叠预制的无支架微组织部件和集成管腔。部分自发融合成一个连续的大组织与灌注通道。可定制的微组织可快速制备至厘米级，并具有持续的功能性能。计算模型的开发和实验验证，以阐明在建成macrotissues对流营养物质运输的灌注率和组织几何形状的影响。结果表明，由人肝细胞微组织构建的大组织在5天内保持几何形状和功能（白蛋白和尿素分泌）。Bio‐P3技术制造具有高细胞数量和密度的大块固体组织，以模拟临床前和临床应用的人体生理学。
Engineered tissues usually fall short of physiological cell densities and sizes, resulting in limited functional performance. Viability of large tissues is constrained by inadequate diffusion‐driven nutrient exchange. Methods to form large viable tissues are lacking and are constrained by diffusion‐driven nutrient exchange. Here, the use of the Bio‐Pick, Place, and Perfuse (Bio‐P3) is reported, an integrated biofabrication‐bioreactor platform that semiautomatically and rapidly assembles physiologically cell‐dense macrotissues with 100 million cells while being actively perfused. The Bio‐P3 grips, aligns, and stacks prefabricated, scaffold‐free microtissue parts with integrated lumens on a perfusable build‐platform. Parts spontaneously fuse into one continuous macrotissue with perfusable channels. Customizable microtissues are rapidly prepared up to centimeter‐scale with sustained functional performance. Computational models are developed and experimentally validated to elucidate the effects of perfusion rate and tissue geometry on convective nutrient transport in built macrotissues. It is shown that macrotissues constructed from human hepatocellular microtissues maintain geometry and function (albumin and urea secretion) over 5 days. The Bio‐P3 technology fabricates massive solid tissues with high cell numbers and densities to mimic human physiology for preclinical and clinical applications.
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