In Vivo Monitoring of Strain and Oxygen in TE Constructs Using MEMS-Based Sensors

使用基于 MEMS 的传感器对 TE 结构中的应变和氧气进行体内监测

• 批准号: 8970271
• 负责人: ROBERT E GULDBERG
• 金额: $ 17.95万
• 依托单位: GEORGIA INSTITUTE OF TECHNOLOGY
• 依托单位国家: 美国
• 财政年份: 2015
• 资助国家: 美国
• 起止时间: 2015-07-01 至 2017-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8970271
• 关键词: Address; Beds; Biosensor; Bone Regeneration; Catheters; Ceramics; Chemicals; Clinical; Complex; Computer Simulation; Cues; Data; Defect; Development; Devices; Diaphyses; Electrical Engineering; Engineering; Engraftment; Environment; Femur; Foundations; Gene Proteins; Goals; Hypoxia; Implant; In Vitro; Intervention; Ischemia; Measurement; Measures; Mechanical Stress; Mechanics; Mediating; Metals; Microfabrication; Modeling; Monitor; Natural regeneration; Oxygen; Oxygen measurement, partial pressure, arterial; Polymers; Pre-Clinical Model; Process; Publishing; Rattus; Regenerative Medicine; Research; Signal Transduction; Silicon; Stem cells; Stress; System; Technology; Testing; Tissue Engineering; Tissues; Wireless Technology; Work; analytical tool; base; biological systems; bone; comparative; design; experience; flexibility; head-to-head comparison; human subject; implantation; improved; in vivo; in vivo regeneration; innovation; miniaturize; minimally invasive; novel; pre-clinical; pressure; prototype; public health relevance; regenerative; repaired; research clinical testing; sample fixation; sensor; temporal measurement; tissue regeneration; tissue trauma

 DESCRIPTION (provided by applicant): Mechanical and oxygen-based cues drive a wide array of developmental, homeostatic, and regenerative processes in many if not all tissues; however, the majority of mechanobiology and hypoxic signaling work has been limited to in vitro and in silico environments due to technical limitations of the analytical tools used in vivo. Advances in microelectromechanical systems (MEMS) have created an opportunity to realize a new class of flexible sensors, suitable for incorporation or implantation into biological systems and tissue engineered constructs. Our long term goal is to advance the understanding of oxygen related signaling and mechanobiology by developing a new class of implantable MEMS sensors. We propose to use these sensors to measure the mechanical and oxygen environment locally within different tissue engineered, regenerative environments. The Allen lab has developed numerous microfabrication and microelectromechanical systems (MEMS) strategies, that have enabled the successful design and development of miniaturized sensors from a variety of materials including silicon, metals, ceramics, and polymers. In preliminary studies, we have shown through both in silico analysis and in vitro prototype testing the ability of sensors to fit the complex design criteria of this proposal. Concurrently, the Guldberg lab has established an in vivo, critically sized, segmental bone defect model in the rat which serves as a test-bed to quantitatively screen the efficacy of novel tissue engineered strategies to repair large bone defects. Local measurements of mechanics and oxygen concentration within the regenerating environment in vivo would significantly improve our understanding of tissue regeneration and the fate of tissue engineered constructs. The complimentary expertise of the two labs in MEMS and regenerative medicine, provide the foundation for an interdisciplinary project to locally characterize key factors during tissue regeneration. The objective of this proposal is to develop MEMS sensors that will measure local mechanical stresses and local oxygen tension within a regenerating tissue environment. The following Specific Aims have been designed to fully develop the MEMS technology and to apply it to an in vivo regeneration model: Aim I - To engineer a minimally invasive, implantable MEMS based sensor to measure oxygen concentration and local stress within a tissue engineered construct. Aim II - To characterize temporal changes in oxygen concentration and local mechanics in a critically sized segmental bone defect model. MEMS based devices offer a unique potential to take continuous measurements in vivo in a minimally invasive manner. This research will bring together outstanding expertise from different fields to engineer an innovative new application of MEMS technology which will significantly advance basic understanding of regenerative processes in addition to improving development and pre-clinical evaluation of tissue engineered constructs.

 描述（由申请人提供）：机械和氧基线索驱动许多（如果不是所有）组织中的各种发育、稳态和再生过程;然而，由于体内使用的分析工具的技术限制，大多数机械生物学和缺氧信号传导工作仅限于体外和计算机模拟环境。微机电系统（MEMS）的进步为实现一类新的柔性传感器创造了机会，该柔性传感器适合于并入或植入生物系统和组织工程构造中。我们的长期目标是通过开发一类新的可植入MEMS传感器来促进对氧相关信号和机械生物学的理解。我们建议使用这些传感器来测量不同组织工程再生环境中的机械和氧气环境。艾伦实验室开发了许多微加工和微机电系统（MEMS）策略，这些策略使得能够成功设计和开发各种材料的小型化传感器，包括硅、金属、陶瓷和聚合物。在初步研究中，我们已经通过计算机分析和体外原型测试显示了传感器的能力， 符合本提案的复杂设计标准。与此同时，Guldberg实验室在大鼠体内建立了一个关键尺寸的节段性骨缺损模型，该模型可作为定量筛选新型组织工程策略修复大骨缺损的有效性的试验平台。在体内再生环境中的力学和氧浓度的局部测量将显着提高我们对组织再生和组织工程构建物的命运的理解。两个实验室在MEMS和再生医学方面的互补专业知识为跨学科项目提供了基础，以在组织再生过程中局部表征关键因素。该提案的目的是开发MEMS传感器，该传感器将测量再生组织环境内的局部机械应力和局部氧张力。以下具体目标旨在充分开发MEMS技术并将其应用于体内再生模型：目标I -设计一种微创、可植入的基于MEMS的传感器，以测量组织工程构造内的氧气浓度和局部应力。目的II -描述临界尺寸节段性骨缺损模型中氧浓度和局部力学的时间变化。基于MEMS的设备提供了以微创方式在体内进行连续测量的独特潜力。这项研究将汇集来自不同领域的优秀专业知识，设计MEMS技术的创新应用，这将大大推进对再生过程的基本理解，以及改善组织工程结构的开发和临床前评估。