Electromechanical Interactions of Gold Nanomaterials with Human Cardiac Cells

金纳米材料与人体心肌细胞的机电相互作用

• 批准号: 2016501
• 负责人: Mehdi Nikkhah
• 金额: $ 55.69万
• 依托单位: Arizona State University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-07-01 至 2024-06-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2016501&HistoricalAwards=false
• 关键词: Electromechanical; Interactions; Gold; Nanomaterials; Human

Nanomaterials have been widely used for a diverse range of applications from environmental to biological engineering and therapeutics. Among different types of nanomaterials, gold nanomaterials are promising candidates because of their minimal toxicity, ease of fabrication, and electrical conductivity. Gold nanomaterials are used in applications such as regenerative medicine, specifically for engineering of electroconductive tissues (e.g. cardiac, nerve or skeletal) that could be used for treatment of trauma, injuries or diseases. However, there are still knowledge gaps regarding mechanistic understanding about interactions between gold nanomaterials with electroactive human heart cells. This research team brings interdisciplinary expertise in biological, environmental and nanotechnology engineering. It aims to synthesize diverse geometries of gold nanomaterials and use 3-dimensionsal hydrogel biomaterials that mimic a porous tissue microenvironment to independently study the biophysical and electrical interactions of nanomaterials with human heart cells at cellular and molecular levels. The project has been carefully designed to broadly impact society through educating the next generation of high school, undergraduate, and graduate students, while bringing synergy among scientists across interdisciplinary fields. This project focuses on the development of a mechanistic and fundamental framework for the interactions of gold nanomaterials with human cardiac cells (i.e. heart cells) that modulate their biological response. The research design is based on a two-fold strategy, through independent assessment of the biophysical and electrical interactions of gold nanomaterials with cardiac cells. First, a library of gold nanomaterials with a wide range of geometries and defined surface chemistries, will be synthesized and then embedded in hydrogel-based scaffolding biomaterials to mimic a porous native-like tissue microenvironment found in the heart. Subsequently, cellular uptake of gold nanomaterials, surface colonization, spreading as well as changes in cytoskeletal structure of the cardiac cells and specific protein markers will be assessed within the nano-enabled hydrogels. Next, gold nanoparticles will be synthesized with different surface functionalities, while maintaining a fixed particle geometry, to specifically isolate the effect of varying conductivity of nanomaterials on the electrophysiological response of cardiac cells. Through these research objectives, the team will test the overarching hypothesis that the mode of interaction of gold nanomaterials with cardiac cells is through two primary independent pathways by which gold nanomaterials influence the cellular-level function and molecular-level response of the cells. These two pathways are biophysical and electrophysiological sensing. The outcome of this study will generate fundamental knowledge for in depth understanding of interactions of conductive nanomaterials with human cells and will further enable better design of nanomaterials for biological and environmental systems. Additionally, the interdisciplinary nature of this study will train the next generation of high school, undergraduate and graduate students, will broadly present the methodology and the outcome of this research to the scientific community and will bring together scientist and collaborators across interdisciplinary fields, ranging from bioengineering to nanotechnology, surface engineering, and cell biology.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.

纳米材料已被广泛应用于从环境到生物工程和治疗的各种应用。在不同类型的纳米材料中，金纳米材料因其毒性小、易于制备和导电性而成为很有前途的候选材料。金纳米材料被用于再生医学等应用，特别是可用于治疗创伤、损伤或疾病的导电组织(例如心脏、神经或骨骼)的工程。然而，关于金纳米材料与电活性人体心脏细胞之间的相互作用的机理理解仍然存在知识空白。这个研究团队带来了生物、环境和纳米技术工程方面的跨学科专业知识。它旨在合成不同几何形状的金纳米材料，并利用模拟多孔组织微环境的三维水凝胶生物材料在细胞和分子水平上独立研究纳米材料与人类心脏细胞的生物物理和电学相互作用。该项目经过精心设计，旨在通过教育下一代高中生、本科生和研究生来广泛影响社会，同时在跨学科领域的科学家之间带来协同效应。该项目的重点是开发金纳米材料与调节其生物反应的人类心脏细胞(即心脏细胞)相互作用的机械和基本框架。这项研究设计基于双重战略，通过独立评估金纳米材料与心脏细胞的生物物理和电学相互作用。首先，将合成一个具有广泛几何结构和定义的表面化学成分的金纳米材料库，然后将其嵌入基于水凝胶的支架生物材料中，以模拟心脏中发现的多孔的天然组织微环境。随后，将在纳米启用的水凝胶中评估细胞对金纳米材料的摄取、表面定植、扩散以及心肌细胞和特定蛋白质标志物的细胞骨架结构的变化。接下来，将合成具有不同表面功能的金纳米颗粒，同时保持固定的颗粒几何形状，以具体隔离纳米材料的不同电导率对心肌细胞电生理反应的影响。通过这些研究目标，该团队将检验最重要的假设，即金纳米材料与心脏细胞的相互作用模式是通过两条主要的独立途径来实现的，通过这两条途径，金纳米材料影响细胞水平的功能和分子水平的反应。这两条途径是生物物理和电生理感知。这项研究的结果将为深入了解导电纳米材料与人类细胞的相互作用提供基础知识，并将进一步为生物和环境系统更好地设计纳米材料。此外，这项研究的跨学科性质将培养下一代高中生、本科生和研究生，将向科学界广泛展示这项研究的方法和结果，并将汇集从生物工程到纳米技术、表面工程和细胞生物学等跨学科领域的科学家和合作者。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Electroconductive Hydrogel Scaffolds to Enhance Maturation of Human iPSC-derived Cardiac Tissues

导电水凝胶支架可促进人 iPSC 来源的心脏组织的成熟

• 发表时间: 2022
• 期刊: Biomedical Engineering Society (BMES
• 作者: Esmaeili, Hamid