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

 描述(申请人提供)：机械和氧基线索在许多组织(如果不是所有组织)中驱动广泛的发育、内稳态和再生过程；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低氧信号传递工作仅限于体外和硅胶环境中。微电子机械系统(MEMS)的进步创造了实现新型柔性传感器的机会，适用于将其整合或植入到生物系统和组织工程结构中。我们的长期目标是通过开发一类新型的植入式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在不同的组织工程和再生环境中测量局部的机械和氧气环境。Allen实验室开发了许多微制造和微电子机械系统(MEMS)策略，成功地设计和开发了使用各种材料(包括硅、金属、陶瓷和聚合物)的微型传感器。在初步研究中，我们已经通过电子分析和体外原型测试证明了传感器的能力 符合本提案的复杂设计标准。与此同时，Guldberg实验室已经在大鼠体内建立了一个临界大小的节段性骨缺损模型，作为一个试验床，定量筛选新的组织工程策略修复大型骨缺损的有效性。在体内对再生环境中的力学和氧气浓度进行局部测量将极大地提高我们对组织再生和组织工程构建的命运的理解。这两个实验室在MEMS和再生医学方面的互补专业知识为一个跨学科项目提供了基础，该项目旨在对组织再生过程中的关键因素进行局部表征。这项建议的目标是开发MEMS传感器，用于测量再生组织环境中的局部机械应力和局部氧分压。为充分开发MEMS技术并将其应用于体内再生模型，设计了以下具体目标：目标I-设计一种基于微创、可植入的MEMS传感器，以测量组织工程结构中的氧浓度和局部应力。目的II-在一个临界大小的节段性骨缺损模型中，表征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活体内进行连续测量的独特潜力。这项研究将汇集不同领域的杰出专业知识，设计MEMS技术的创新应用，除了改善组织工程结构的开发和临床前评估外，还将极大地促进对再生过程的基本了解。

 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.