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

芯片上器官工程可能会给新的化合物筛选和生物标记物发现带来革命性的变化。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，如血管生成，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对立的标准结合在一起：血管系统的渗透性和机械稳定性，在用于芯片上器官工程的单一微制聚合物支架中。然而，聚合物结构的组装需要多个光刻步骤和手工逐层组装。尽管这种方法有很大的潜力，但使用目前的微制造方法无法实现规模化。在这里，我们建议开发一种基于3D打印的新的添加剂制造技术，以直接、自动和快速地打印具有可控制的nm-um孔隙率和嵌入的血管系统的准备用于3D器官自组装的聚合物支架。目前还没有标准化的芯片上器官制造技术，而加法制造是满足这一未得到满足的需求的最有前途的技术。我们将开发新的弹性聚合物作为墨水和立体摄影方法，将其3D打印成封闭管腔的器官支架。我们将设计标准孔板大小的惰性培养平台，每个平台将安装一个3D可生物降解的微型器官支架，准备好细胞种植和无泵灌流。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，迫切需要用于其功能的新的生物标记物。我们将把导电聚合物集成到芯片上的心脏中，用于驱动和场电位传感。我们的支持组织将能够通过使用芯片上器官来开发新的分析(PHOTON)、识别新的肝功能衰竭生物标记物(核技术)和心力衰竭生物标记物(塔拉生物系统)以及依赖芯片上器官进行其内部药物测试项目(核技术和塔拉生物系统)来利用这一合作。他们共同提供超过19万美元的实物捐助来支持该项目。

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.