Collaborative Research: EAGER: Biomanufacturing: Bioengineering of 3-dimensional brain surrogate tissue models

合作研究：EAGER：生物制造：3 维脑替代组织模型的生物工程

• 批准号: 1547806
• 负责人: David Kaplan
• 金额: $ 15万
• 依托单位: Tufts University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-09-01 至 2017-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1547806&HistoricalAwards=false
• 关键词: Collaborative; Research; EAGER; Biomanufacturing; Bioengineering

PI: Demirci, UtkanProposal Number: 1547791PI: Kaplan, David L. Proposal Number: 1547806 The coordinated function in the brain of billions of neurons in dense and entangled networks can be seen as the epicenter of our unique higher consciousness, as well as of our vulnerability to debilitating diseases, such as schizophrenia, autism and Alzheimer's. The investigators propose a unique approach of sound waves and silk protein biomaterials, to recreate the complex three-dimensional brain network structures in a small dish, and use them to investigate their response to a laboratory model of brain concussion damage. With these studies, the investigators aspire to demonstrate how these constructs may help scientists better understand the workings of the brain in healthy and diseased states.The complexity of the brain poses a large roadblock for scientists to examine molecular, cellular and circuit level behavior of brain physiology. Novel approaches and technologies are needed that complement and advance the existing in vivo, ex vivo and in vitro approaches. The goal of the proposed research is to develop a new flexible bioprinting platform for the in vitro fabrication of 3-dimensional (3D) neural tissue constructs that faithfully mimic the biological complexity, development, architecture and function of 3D circuits present in the brain. The key innovations include the strategy of acoustic biopatterning and silk protein scaffolds for encapsulating neurons in long-lived, 3D multilayered architectures. To prototype and validate the construct, the investigators propose in the first aim to create 6-layer cortical circuits built of primary neurons. In the second aim, they will examine the physiology of the 3D circuit tissues using a comprehensive neuro-technological tool-box. Electrophysiology, fluorescence imaging, genomics and proteomics approaches will be employed to evaluate functional and structural milestones of the developing in vitro 3-D neural circuits, including a brain damage disease model. This radically different approach for investigating brain physiology and pathophysiology has the potential to provide new tools for neuroscience, the utility of which extends to other fields because of the general applicability of the proposed advanced biomanufacturing approaches. The broader impact of this proposal includes the participation of high school, undergraduate and graduate level scientists in research at the intersection of neuroscience, tissue engineering and biomanufacturing, thus presenting a useful platform for the training of interdisciplinary scientists.

PI: Demirci, UtkanProposal Number: 1547791PI: Kaplan, David L. Proposal Number: 1547806 The coordinated function in the brain of billions of neurons in dense and entangled networks can be seen as the epicenter of our unique higher consciousness, as well as of our vulnerability to debilitating diseases, such as schizophrenia, autism and Alzheimer's.研究人员提出了一种独特的声波和丝绸蛋白生物材料的方法，以在小菜中重新创建复杂的三维脑网络结构，并使用它们来研究其对脑脑震荡损害实验室模型的反应。通过这些研究，研究人员渴望证明这些结构如何帮助科学家更好地理解健康和患病状态下的大脑的起作用。需要采用新颖的方法和技术来补充并推进现有的体内，体内和体外方法。拟议的研究的目的是开发一个新的柔性生物打印平台，用于体外制造3维（3D）神经组织构建体，该构建体忠实地模仿了大脑中存在的3D电路的生物学复杂性，发展，结构和功能。关键创新包括声学生物原子和丝绸蛋白支架的策略，以封装长寿命，3D多层体系结构中的神经元。为了原型和验证构建体，研究人员在第一个目的提出了创建由原代神经元建造的6层皮质电路。在第二个目标中，他们将使用全面的神经技术工具箱检查3D电路组织的生理。电生理学，荧光成像，基因组学和蛋白质组学方法将采用用于评估正在发展的体外3-D神经回路的功能和结构里程碑，包括脑损伤疾病模型。这种研究脑生理和病理生理学的根本不同的方法具有为神经科学提供新工具的潜力，由于拟议的先进生物制造方法的一般适用性，该神经科学的实用性扩展到了其他领域。该提案的更广泛影响包括在神经科学，组织工程和生物制造的交集中，高中，本科和研究生一级的科学家参与研究，从而为训练跨学科科学家提供了有用的平台。