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

使用可生物降解的弹性聚合物增材制造芯片器官

• 批准号: 506689-2017
• 负责人: Radisic, Milica
• 金额: $ 13.09万
• 依托单位: University of Toronto
• 依托单位国家: 加拿大
• 项目类别: Strategic Projects - Group
• 财政年份: 2018
• 资助国家: 加拿大
• 起止时间: 2018-01-01 至 2019-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=662855
• 关键词: Additive; manufacturing; organs; chip; using

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.**********

芯片上器官工程可以彻底改变新化合物筛选和生物标志物发现。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，如血管系统，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，在一个用于器官芯片工程的基于微制造聚合物的支架中。 然而，聚合物结构的组装需要多个光刻步骤和手动逐层组装。尽管这种方法具有很大的潜力，但使用当前的微制造方法不可能进行缩放。在这里，我们建议开发一种基于3D打印的新型增材制造技术，以直接，自动和快速打印聚合物支架，具有受控的nm-um孔隙率和嵌入的脉管系统，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，增材制造是满足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和立体印刷方法，用于将其3D打印成具有封闭管腔的器官支架。我们将设计惰性培养平台，其尺寸与标准孔板相同，每个孔板都配有一个3D可生物降解的微型器官支架，可用于细胞接种和无泵灌注。心脏和肝脏组织将基于人类细胞生长，因为它们经常受到药物毒性的影响，并且迫切需要用于其功能的新生物标志物。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），识别新的肝功能衰竭生物标志物（Nucro-technics）和心力衰竭生物标志物（塔拉生物系统），以及依靠器官芯片进行内部药物测试项目（Nucro-technics和塔拉）。他们共同为该项目提供了超过190 000美元的实物捐助。