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

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，但研究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使用培养皿中培养的细胞进行的。虽然此类研究提供了大量关于纳米材料的物理、机械和化学特性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。该项目旨在创建一个通过新型生物打印技术生成的工程三维人体心脏组织模型，并利用该模型研究纳米粒子对心脏的影响。 该项目的成功将消除在纳米材料的组织和器官毒性研究中对昂贵的动物模型系统的需求。该项目的高度跨学科性质将涉及跨越传统界限对学生进行培训，提供令人兴奋的主题，包括生物打印、组织工程、纳米技术和纳米粒子的生物相互作用。此外，该项目还将促进跨专业和学术发展多个阶段的广泛培训，包括不同背景的研究生、本科生和高中生。 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 3 维生物打印创建的 3 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型人体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于合成一套具有不同成分和表面涂层的单分散纳米颗粒。将进行纳米心脏相互作用的评估，以研究这些纳米粒子对细胞活力、形态、基因表达和心脏力输出的影响。通过该项目，将建立使用这些工程人体组织模型进行纳米毒性研究的可行性。该项目属于高风险项目。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 3 维人体组织的生物相容性提供重要的见解。该项目将利用人类诱导多能干细胞衍生的心肌细胞，进一步揭示这些纳米粒子的个体效应。调查人员处于有利位置且具有独特的优势来解决这些问题。首席研究员是 3 维生物打印领域的先驱，在生物材料、生物打印和组织工程的前沿研究方面拥有出色的记录。联合首席研究员是研究纳米材料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能够跨越传统界限进行培训，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，该项目还将促进培训不同背景的研究生、本科生和高中生。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

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.