计算模型旨在加速微流体生物打印
人体器官的移植为患有严重疾病的人提供了关键的生命线，但是器官太少了：仅在美国，目前有112,000多人正在等待移植。3D打印器官的承诺是解决此短缺的一种可能解决方案，但充满了复杂性和技术障碍，限制了可以打印的器官的类型。史蒂文斯理工学院的研究人员现在通过利用数十年历史的技术来重现任何组织类型，从而推动了这些障碍。
这项工作由史蒂文斯（Stevens）的机械工程系副教授罗伯特·张（Robert Chang）领导，史蒂文斯（Schaefer）工程与科学学院的机械工程系副教授，可以随时开放3D打印任何器官的途径，甚至直接在开放的伤口上皮肤。
“Creating new organs to order and saving lives without the need for a human donor will be an immense benefit to healthcare,” said Robert Chang, whose work appears in the April issue ofScientific Reports。“However, reaching that goal is tricky because printing organs using “bio-inks” — hydrogels laden with cultured cells — requires a degree of fine control over the geometry and size of printed microfiber that current 3D printers simply can’t achieve.”
Chang and his team, including Ahmadreza Zaei, first author and doctoral candidate in Chang’s lab, hope to change that by fast-tracking a new 3D printing process that uses microfluidics — the precise manipulation of liquids through tiny channels — to operate at a far smaller scale than has been possible. “The recent publication aims to improve the controllability and predictability over the structure of the fabricated microtissues and microfibers enabled by microfluidic bioprinting technology,” said Zaeri.
Most current 3D bio-printers are extrusion-based, squirting bio-ink out of a nozzle to create structures about 200 microns — around a tenth as wide as a strand of spaghetti. A microfluidics-based printer could print biological objects measuring on the order of tens of micrometers on par with the single cellular scale.
“The scale is very important, because it affects the biology of the organ,” said Chang. “We’re operating at the scale of human cells, and that lets us print structures that mimic the biological features we’re trying to replicate.”
Besides operating on a smaller scale, microfluidics also enables multiple bio-inks, each containing different cells and tissue precursors, to be used interchangeably within a single printed structure, in much the same way that a conventional printer combines colored inks into a single vivid image.
这很重要，因为尽管研究人员已经通过鼓励组织在3D打印的脚手架上生长而创建了简单的器官，例如膀胱，但更复杂的器官（例如肝脏和肾脏）需要精确组合许多不同的细胞类型。Chang说：“能够以这种规模运行，同时精确地混合生物墨水，这使我们有可能再现任何组织类型。”
缩小3D生物印刷需要艰苦的研究，以准确弄清楚不同的过程参数（例如通道结构，流速和流体动力学）如何影响印刷生物学结构的几何形状和材料特性。为了简化该过程，Chang的团队创建了一个微流体打印头的计算模型，使他们能够调整设置和预测结果，而无需进行艰苦的现实世界实验。
“Our computational model advances a formulaic extraction that can be used to predict the various geometrical parameters of the fabricated structures extruded from the microfluidic channels,” said Zaeri.
The team’s computational models accurately predicted the results of real-world microfluidic experiments, and Chang is using his model to guide experiments on the ways that biological structures with varies geometries can be printed. The results of this research work can be used in the printing of combined multiple cell-types bio-ink that can replicate the tissue with gradients geometrical and compositional properties found at the intersection of bone and muscle.
Chang is also exploring using microfluidic-enabled 3D printing for the in-situ creation of skin and other tissues, enabling patients to have replacement tissues printed directly into a wound. “This technology is still so new that we don’t know precisely what it will enable,” he said. “But we know it will open the door to creating new structures and important new types of biology.”
Reference:Zaeri A，Zgeib R，Cao K，Zhang F，Chang RC。基于微流体的生物打印参数对微纤维几何结果的影响的数值分析。Sci Rep。2022; 12（1）：3364。doi：10.1038/S41598-022-07392-0
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