Multifunctional 3D Bioelectronic and Microfluidic Hybrid Systems for Online Monitoring, Regulation, and Vascularization of Organoids

用于在线监测、调节和类器官血管化的多功能 3D 生物电子和微流体混合系统

• 批准号: 10688234
• 负责人: Xueju Wang
• 金额: $ 19.6万
• 依托单位: UNIVERSITY OF CONNECTICUT STORRS
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-09-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10688234
• 关键词: 3-Dimensional; Alzheimer' s Disease; Award; Behavior; Biochemical; Biological; Biological Models; Biomimetics; Biosensing Techniques; Blood Vessels; Brain; Brain Mapping; Cells; Characteristics; Collaborations; Communities; Culture Media; Development; Devices; Dimensions; Disease; Drug Screening; Drug toxicity; Electric Stimulation; Electronics; Electrophysiology (science); Evaluation; Geometry; Goals; Heart; Heterogeneity; Human; Hybrids; In Vitro; Investigation; Kidney; Light; Location; Longevity; Lung; Measurement; Mechanics; Microelectrodes; Microfluidics; Monitor; National Institute of Biomedical Imaging and Bioengineering; Neurosciences; Neurosciences Research; Online Systems; Optics; Organogenesis; Organoids; Oxygen; Pattern; Performance; Pluripotent Stem Cells; Porosity; Property; Public Health; Reaction Time; Regenerative Medicine; Regulation; Research; Resolution; Route; Structure; Surface; System; Systems Integration; Techniques; Thinness; Tissue Engineering; Tissue Model; Tissues; Vascularization; Work; adult stem cell; bioelectronics; biomaterial compatibility; body system; density; design; flexibility; improved; in vivo; induced pluripotent stem cell; innovation; interest; light emission; lithography; miniaturize; multi-electrode arrays; multidisciplinary; multimodality; nanofabrication; nervous system disorder; neural patterning; neural stimulation; neurodevelopment; new technology; nutrition; optogenetics; personalized medicine; pharmacologic; polydimethylsiloxane; prevent; sensor; small molecule; spatiotemporal; tissue culture; two-dimensional

PROJECT SUMMARY/ABSTRACT Human organoids are miniaturized model systems of organs produced by three-dimensional (3D) cultures of tissue-resident-adult stem cells (ASCs) or pluripotent stem cells (PSCs) in vitro. They have emerged as a promising platform for modeling tissue development and disease, personalized medicine development, drug screening and drug toxicity investigations. Despite their great potential, current human organoids suffer from immature structure and functionality, limited heterogeneity, as well as limited accessible readouts for organoid evaluation. For example, detailed investigations of these 3D biosystems, such as 3D electrophysiological mapping for brain and heart organoids, cannot be achieved using conventional approaches such as two- dimensional (2D) multi-electrode arrays (MEAs) for modulation and multimodal sensing. Furthermore, most current biosystems lack stable and mature vascularization that exists in vivo, which poses challenges to controlled delivery of oxygen, nutrition, and molecules like neural patterning factors to enhance organoid size, lifespan, and complexity. Our goal is to develop a soft electronic/microfluidic hybrid 3D network for online monitoring, regulation, and vascularization of human organoids. The resulting system will integrate separately addressable electrical, optical, electrochemical, and thermal sensors and stimulators of designated locations with 3D biomimetic microvascular networks for simultaneous sensing, stimulation, and well-controlled delivery of molecules into deep tissues to study tissue development and modulation. We will achieve this goal through pursuing three specific aims: (1) Develop multifunctional 3D electronic networks with high spatiotemporal resolution for online monitoring and regulation of organoid function, (2) Develop biomimetic 3D microvascular networks for the vascularization of 3D tissues and integrate them with 3D electronic networks into a hybrid system, and (3) Evaluate the efficiency and functional robustness of the integrated system in vitro using brain organoids as an example. Our proposed multifunctional hybrid system incorporates the following notable innovative features: 1) Soft, stretchable 3D networks for electrical, optical, electrochemical, and thermal sensing and stimulation of human organoids, 2) Biomimetic 3D microvascular networks for the vascularization of human organoids, 3) Fully integrated electronics and microfluidics networks as a micro-lab for investigating various induced and natural behaviors of human organoids. This work will create a new route to study neurodevelopment and neurological disorders through simultaneous monitoring, regulation, and vascularization of brain organoids throughout their 3D interior, which is of broad potential interest to the neuroscience community. In addition, the developed 3D hybrid system can be applied to other types of organoids, including heart, lung, and kidney for in vitro studies of related diseases.

项目摘要/摘要 人体器官是由人体器官的三维(3D)培养产生的器官的微型模型系统 组织驻留-成体干细胞(ASCs)或体外多能干细胞(PSCs)。它们已经成为一种 组织发育和疾病、个性化药物开发、药物建模的有前途的平台 筛查和药物毒性调查。尽管它们具有巨大的潜力，但目前的人类有机体受到 不成熟的结构和功能，有限的异质性，以及有限的可访问有机化合物读数 评估。例如，对这些3D生物系统的详细研究，如3D电生理 大脑和心脏器官的映射，不能使用常规方法实现，例如两个- 用于调制和多模式传感的维(2D)多电极阵列(MEA)。此外，大多数 目前的生物系统缺乏体内存在的稳定和成熟的血管形成，这对 氧气、营养和神经模式因子等分子的受控输送，以增加有机物的大小， 寿命和复杂性。我们的目标是开发一种用于在线的软电子/微流体混合3D网络 人体器官的监测、调节和血管化。由此产生的系统将单独集成 指定位置的可寻址的电、光、电化学和热传感器和刺激器 具有3D仿生微血管网络，可同时进行传感、刺激和良好控制的输送 分子进入深层组织以研究组织发育和调节。我们将通过以下方式实现这一目标 追求三个具体目标：(1)发展具有高度时空特性的多功能3D电子网络 器官功能在线监测和调节的解决方案，(2)开发仿生三维微血管 用于3D组织血管化的网络，并将它们与3D电子网络集成成混合体 系统，以及(3)在体外用脑评估集成系统的效率和功能稳健性 以有机化合物为例。我们建议的多功能混合系统包含以下值得注意的 创新功能：1)柔软、可扩展的3D网络，用于电、光、电化学和热传感 和对人体器官的刺激，2)用于人体血管形成的仿生三维微血管网络 有机化合物，3)完全集成的电子和微流体网络，作为研究各种 人类类器官的诱导行为和自然行为。这项工作将为研究神经发育开辟一条新的途径 通过同时监测、调节和脑组织血管化而引起的神经疾病 在其3D内部，这是神经科学界广泛潜在的兴趣。此外， 所开发的3D杂交系统可应用于其他类型的有机化合物，包括心脏、肺和肾脏 相关疾病的体外研究。