Additive manufacturing of organs-on-a-chip using biodegradable elastomeric polymers

器官芯片工程可以彻底改变新的化合物筛选和生物标志物的发现。然而，目前的平台只能复制非常有限的一组器官，并且缺乏许多关键的器官功能，如脉管系统，这极大地限制了它们的潜力。最近，我们开发了AngioChip技术，使我们能够将两个看似相反的标准结合起来：血管的渗透性和机械稳定性，在一个用于器官芯片工程的单个微制造聚合物支架中。然而，聚合物结构的组装需要多个光刻步骤，并且需要手工逐层组装。尽管这种方法有很大的潜力，但使用目前的微加工方法是不可能缩放的。在这里，我们提出了一种基于3D打印的新型增材制造技术，可以直接，自动和快速地打印聚合物支架，具有可控的纳米孔隙度，并具有嵌入式血管系统，为3D器官自组装做好准备。目前还没有标准化的器官芯片制造技术，而增材制造是解决这一未满足需求的最有前途的技术。我们将开发新的弹性体聚合物作为油墨，并采用立体印刷方法将其3D打印成具有封闭腔的器官支架。我们将设计具有标准孔板尺寸的惰性培养平台，每个平台都将配备一个3D可生物降解的微型器官支架，为细胞播种和无泵灌注做好准备。心脏和肝脏组织将在人类细胞的基础上生长，因为它们经常受到药物毒性的影响，而且迫切需要新的生物标志物来检测它们的功能。我们将在芯片上的心脏中加入导电聚合物，用于驱动和场电位传感。我们的支持组织将能够利用这种合作，通过使用器官芯片开发新的分析（Photon），识别新的肝衰竭生物标志物（Nucro-technics）和心力衰竭生物标志物（TARA Biosystems），以及依靠器官芯片进行内部药物测试项目（Nucro-technics和TARA）。他们共同为该项目提供了超过19万美元的实物捐款。

Organ-on-a-chip engineering could revolutionize new compound screening and biomarker discovery. However, current platforms only reproduce a very limited set of organs and lack many critical organ functions such as vasculature, which greatly limits their potential. Recently, we developed AngioChip technology that enabled us to marry two seemingly opposing criteria: permeability and mechanical stability of the vasculature, in a single microfabricated polymer based scaffold for organ-on-a-chip engineering. However, the assembly of the polymer structures necessitated multiple photolithography steps, and manual, layer-by-layer assembly. Despite the great potential of this approach, scaling is not possible using current microfabrication methods. Here, we propose to develop a novel additive manufacturing technology based on 3D printing to directly, automatically and rapidly print polymer scaffolds, with controlled nm-um porosity and with an embedded vasculature ready for 3D organ self-assembly. There are currently no standardized organ-on-a-chip manufacturing technologies, and additive manufacturing is the most promising technology for this unmet need. We will develop new elastomeric polymers to serve as inks and a stereolitography approach for their 3D printing into organ-scaffolds with enclosed lumens. We will design inert cultivation platforms with the dimensions of standard well plates that will each be fitted with a 3D biodegradable mini-organ scaffold ready for cell seeding and pump-free perfusion. Heart and liver tissue will be grown based on human cells, since they are often affected by drug toxicities and novel biomarkers for their functions are critically needed. We will incorporate conductive polymers into the heart-on-a-chip for actuation and field potential sensing. Our supporting organizations will be able to capitalize on this collaboration by using organs-on-a-chip for development of new analytics (Photon), identification of new liver-failure biomarkers (Nucro-technics) and heart-failure biomarkers (TARA Biosystems) as well as relying on organs-on-a-chip for their in-house drug testing projects (Nucro-technics and TARA). Together, they are supporting the project with over $190,000 of in-kind contributions.