EAGER: Understanding Nano-Cardio Interactions Using 3D Bioprinted Human Heart Tissue

EAGER：使用 3D 生物打印人体心脏组织了解纳米心脏相互作用

• 批准号: 1903933
• 负责人: Shaochen Chen
• 金额: $ 20万
• 依托单位: University of California-San Diego
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2019
• 资助国家: 美国
• 起止时间: 2019-07-01 至 2022-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1903933&HistoricalAwards=false
• 关键词: EAGER; Understanding; Nano; Cardio; Interactions

While nanotechnology is revolutionizing many industry sectors and having significant impact to our daily lives, investigating the potential negative impacts of nanomaterials becomes ever more important. Most studies that focus on understanding potential health effects are carried out with cells cultured in a petri-dish. While such studies have provided a wealth of information about the importance of nanomaterial's physical, mechanical, and chemical properties in toxicity to cells, they inform less about the interactions of the nanoparticles with human tissues and organs. This project aims to create an engineered 3-dimensional human heart tissue model generated by a novel bioprinting technique, and to use this model to study the impact of nanoparticles on the heart. Success of this this project will eliminate the need for expensive animal model systems in studies of tissue and organ toxicity to nanomaterials. The highly interdisciplinary nature of the project will involve training students across the traditional boundaries, offering exciting topics including bioprinting, tissue engineering, nanotechnology, and biological interactions of nanoparticles. Also, the project will facilitate training broadly across multiple stages of professional and academic development by including graduate students, undergraduate students, and high school students of diverse backgrounds. Technically, this project will be the first attempt in the field to investigate how nanoparticles interact with 3-dimensional human heart tissues, created by 3-dimensional bioprinting. The first research task aims to establish the bioprinted microscale human heart tissue model and evaluate cell alignment, morphology, gene expression, and cardiac function. The second research task will focus on the synthesis of a suite of monodispersed nanoparticles with varying compositions and surface coatings. Assessment of nano-cardio interactions will be carried out to investigate the effects of these nanoparticles on cell viability, morphology, gene expression, and cardiac force output. From this project, the feasibility of using these engineered human tissue models for nanotoxicity studies will be established. The project is of high-risk. But if successful, the outcomes of the project will lead to high reward since it will provide significant insights into the biocompatibility of nanoparticles to 3-dimensional human tissues. Using human induced pluripotent stem cells derived cardiomyocytes, the project will further reveal individual effects of these nanoparticles. The investigators are well situated and uniquely positioned to tackle these issues. The principal investigator is a pioneer in 3-dimensional bioprinting with an excellent track record for cutting-edge research in biomaterials, bioprinting, and tissue engineering. The co-principal investigator is a leading expert in studying the environmental and health implications of nanomaterials. Such a unique collaboration will lead to transformative results. The highly interdisciplinary nature of the project will enable student training across the traditional boundaries, offering exciting topics including biomanufacturing, nanotechnology and biological interactions of nanoparticles. Also, the project will facilitate training graduate students, undergraduate students, and high school students of diverse backgrounds.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.

虽然纳米技术正在彻底改变许多行业，并对我们的日常生活产生重大影响，但调查纳米材料的潜在负面影响变得越来越重要。大多数专注于了解潜在健康影响的研究都是用培养皿中培养的细胞进行的。虽然这些研究提供了大量关于纳米材料的物理，机械和化学性质对细胞毒性的重要性的信息，但它们对纳米颗粒与人体组织和器官的相互作用的了解较少。该项目旨在通过一种新的生物打印技术创建一个工程化的三维人体心脏组织模型，并使用该模型研究纳米颗粒对心脏的影响。 该项目的成功将消除在研究纳米材料的组织和器官毒性时对昂贵的动物模型系统的需要。该项目的高度跨学科性质将涉及跨越传统界限培训学生，提供令人兴奋的主题，包括生物打印，组织工程，纳米技术和纳米颗粒的生物相互作用。此外，该项目将促进培训广泛跨越多个阶段的专业和学术发展，包括研究生，本科生和高中学生的不同背景。 从技术上讲，该项目将是该领域首次尝试研究纳米颗粒如何与三维生物打印创建的三维人体心脏组织相互作用。第一项研究任务旨在建立生物打印的微尺度人类心脏组织模型，并评估细胞排列，形态，基因表达和心脏功能。第二个研究任务将集中在合成一套单分散的纳米粒子与不同的组成和表面涂层。将进行纳米心脏相互作用的评估，以研究这些纳米颗粒对细胞活力、形态、基因表达和心力输出的影响。通过该项目，将确定使用这些工程化人体组织模型进行纳米毒性研究的可行性。该项目具有高风险性。但如果成功，该项目的成果将带来高额回报，因为它将为纳米颗粒与三维人体组织的生物相容性提供重要见解。使用人类诱导多能干细胞衍生的心肌细胞，该项目将进一步揭示这些纳米颗粒的个体效应。调查人员所处的位置很好，处于处理这些问题的独特地位。首席研究员是三维生物打印的先驱，在生物材料，生物打印和组织工程的前沿研究方面有着出色的记录。共同首席研究员是研究纳米材料对环境和健康影响的领先专家。这种独特的合作将带来变革性的结果。该项目的高度跨学科性质将使学生的培训跨越传统的界限，提供令人兴奋的主题，包括生物制造，纳米技术和纳米粒子的生物相互作用。此外，该项目将有助于培养研究生，本科生和高中生的不同背景。该奖项反映了NSF的法定使命，并已被认为是值得支持的评估使用基金会的智力价值和更广泛的影响审查标准。

项目成果

3D Printing of a Biocompatible Double Network Elastomer with Digital Control of Mechanical Properties

• DOI: 10.1002/adfm.201910391
• 发表时间: 2020-02
• 期刊: Advanced Functional Materials
• 影响因子: 19
• 作者: Pengrui Wang;D. Berry;Zhaoqiang Song;Wisarut Kiratitanaporn;Jacob Schimelman;A. Moran;F. He;B. Xi;S. Cai;Shaochen Chen

Direct 3D bioprinting of cardiac micro-tissues mimicking native myocardium

• DOI: 10.1016/j.biomaterials.2020.120204
• 发表时间: 2020-10-01
• 期刊: BIOMATERIALS
• 影响因子: 14
• 作者: Liu, Justin;Miller, Kathleen;Chen, Shaochen
• 通讯作者: Chen, Shaochen

3D Bioprinting of complex tissue in vitro: state-of-the-art and future perspectives

体外复杂组织的 3D 生物打印：最先进的技术和未来的前景

• 发表时间: 2022
• 期刊: Archives of toxicology
• 影响因子: 6.1
• 作者: Y. Xiang, K. Miller

High throughput direct 3D bioprinting in multiwell plates

• DOI: 10.1088/1758-5090/ab89ca
• 发表时间: 2021-04-01
• 期刊: BIOFABRICATION
• 影响因子: 9
• 作者: Hwang, Henry H.;You, Shangting;Chen, Shaochen
• 通讯作者: Chen, Shaochen