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 人体器官是由三维（3D）培养物产生的器官的微型模型系统 在体外，组织居民的干细胞（ASC）或多能干细胞（PSC）。他们已经成为一个 建模组织发育和疾病，个性化医学开发，药物的有前途的平台 筛查和药物毒性研究。尽管他们的潜力很大，但目前的人类类器可以遭受 未成熟的结构和功能性，有限的异质性以及有限的类器官读数 评估。例如，对这些3D生物系统的详细研究，例如3D电生理学 使用常规方法（例如两种方法）无法实现大脑和心脏器官的映射 尺寸（2D）多电极阵列（MEA）用于调制和多模式传感。此外，大多数 当前的生物系统缺乏体内存在的稳定和成熟的血管化，这给挑战带来了挑战 氧气，营养和分子（如神经模式因子）的控制递送，以增强器官大小， 寿命和复杂性。我们的目标是开发用于在线的软电子/微流体混合3D网络 人体器官的监测，调节和血管化。最终的系统将单独集成 指定位置的可寻址电气，光学，电化学和热传感器以及刺激器 具有3D仿生微血管网络，用于同时感测，刺激和良好的传递 分子进入深组织以研究组织发育和调节。我们将通过 追求三个特定目标：（1）开发具有高时空的多功能3D电子网络 用于在线监测和调节器官功能的分辨率，（2）发展仿生3D微血管 3D组织血管化的网络，并将它们与3D电子网络集成到混合动力区 系统，（3）使用大脑在体外评估集成系统的效率和功能鲁棒性 类器官为例。我们提出的多功能混合系统结合了以下著名 创新功能：1）用于电气，光学，电化学和热传感的柔软，可拉伸的3D网络 和人体器官的刺激，2）仿生3D微血管网络，用于人类血管化 器官，3）完全集成的电子和微流体网络作为微型LAB，用于研究各种 人类器官的诱导和自然行为。这项工作将创建一条新的研究神经发育的途径 和神经系统疾病通过同时监测，调节和血管化 在整个3D内部，这是神经科学界的广泛潜在兴趣。另外， 开发的3D混合动力系统可以应用于其他类型的类器官，包括心脏，肺和肾脏 相关疾病的体外研究。