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/2
• 负责人: Molly Stevens
• 金额: --
• 依托单位: University of Oxford
• 依托单位国家: 英国
• 项目类别: Fellowship
• 财政年份: 2024
• 资助国家: 英国
• 起止时间: 2024 至 无数据
• 项目状态: 未结题
• 来源: https://gtr.ukri.org/projects?ref=EP%2FX02721X%2F2
• 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.

工程化离体心脏组织在心血管药物开发的背景下获得了越来越多的关注。它们作为一线工具提供了很大的希望，可以补充甚至用作某些动物药物评价的替代品。然而，它仍然是一个持续的挑战，开发3D工程离体心肌模型，更接近地重演天然心脏组织。该组织由各向异性的多层结构组成，其在调节心脏的独特生物力学行为中起关键作用。相比之下，大多数当前的芯片上心脏模型在2D平坦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打印的各向异性心脏芯片，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螺旋纱和光固化水凝胶的磁控的远程磁传导生物墨水，以诱导hiPSC衍生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各向异性的多层心肌组织。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，我们打算将所制造的组织集成到微流体芯片中。有了这种芯片上的心脏，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，本项目旨在提供一个新的心脏组织平台，用于快速，高通量的药物筛选与自动控制和实时分析。