Development of a 3D-printed anisotropic heart-on-a-chip for drug screening applications

开发用于药物筛选应用的 3D 打印各向异性芯片心脏

• 批准号: EP/X02721X/1
• 负责人: Molly Stevens
• 金额: $ 26万
• 依托单位: Imperial College London
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2023
• 资助国家: 英国
• 起止时间: 2023 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX02721X%2F1
• 关键词: Development; 3D; printed; anisotropic; heart

Engineered ex vivo cardiac tissues have garnered increasing attention in the context of cardiovascular drug development. They offer great promise as first-line tools that can complement or even be used as proxies for some of the drug evaluations carried out with animals. However, it remains an ongoing challenge to develop 3D engineered ex vivo cardiac muscle models that more closely recapitulate native cardiac tissue. This tissue consists of an anisotropic multilayer structure, which plays a key role in regulating the unique biomechanical behaviour of the heart. In contrast, most of the current heart-on-a-chip models employ a single cardiac cell layer on a 2D flat substrate. In this project (HEARTCHIP), we propose to develop a 3D printed anisotropic heart-on-a-chip as an ex vivo acute hypoxia model for CVD drug screening. We will prepare a remote magnetic conductive bioink based on magnetic-control of short nanofiber yarns and photocurable hydrogels to induce the organization and differentiation of hiPSC-derived cardiomyocytes. We will then use a gel-in-gel 3D bioprinting approach to fabricate a 3D anisotropic, multi-layered cardiac muscle tissue. In addition, to provide automated control of culture conditions and real-time measurement of cell physiological responses, we intend to integrate the as-fabricated tissue into a microfluidic chip. With this heart-on-a-chip, we aim to perform high-throughput drug tests in the condition of acute hypoxia. Hence, this project aims to provide a new platform of cardiac tissue for rapid, high-throughput drug screening with automated control and real-time analysis.

在心血管药物开发的背景下，工程离体心脏组织已引起越来越多的关注。它们作为一线工具提供了巨大的前景，可以补充甚至用作某些动物药物评估的代理。然而，开发更接近地再现天然心脏组织的 3D 工程离体心肌模型仍然是一个持续的挑战。这种组织由各向异性多层结构组成，在调节心脏独特的生物力学行为中发挥着关键作用。相比之下，目前大多数心脏芯片模型都在二维平面基底上采用单个心脏细胞层。在这个项目（HEARTCHIP）中，我们建议开发一种 3D 打印的各向异性芯片心脏，作为 CVD 药物筛选的离体急性缺氧模型。我们将制备一种基于短纳米纤维纱线和光固化水凝胶磁控的远程磁导生物墨水，以诱导 hiPSC 来源的心肌细胞的组织和分化。然后，我们将使用凝胶中凝胶 3D 生物打印方法来制造 3D 各向异性、多层心肌组织。此外，为了提供培养条件的自动控制和细胞生理反应的实时测量，我们打算将制造的组织集成到微流控芯片中。借助这种芯片心脏，我们的目标是在急性缺氧条件下进行高通量药物测试。因此，该项目旨在提供一个新的心脏组织平台，用于快速、高通量的药物筛选，并具有自动化控制和实时分析功能。