BioMEMs Sensor for Monitoring Fracture Healing

描述（由申请人提供）：美国人口每年治疗近800万例长骨骨折。大约10%的骨折不能正常愈合。许多这些骨不连或假关节的发生是由于严重或群体性（高度碎裂）的情况没有经过稳定的（膜内骨化）愈合途径。早期发现异常愈合将允许使用更新的非侵入性翻修策略，以及简化更开放翻修程序的技术要求。不幸的是，在骨折部位的标准影像学信息无法区分愈合途径的早期，骨折异常愈合的过程不容易诊断。我们假设，在至关重要的早期阶段，愈合可以通过监测植入的硬件力学来确定。这一假设利用了先前证明的现象，即随着愈合的进行，软组织痂和新形成的骨逐渐承担部分负荷，从而减少了植入硬件的负担（和相关的应变）。因此，为了解决早期识别异常骨折愈合的关键需求，我们开发了一种无线、感应供电（无可植入电源）、生物相容性微机电传感器（bioMEMS），它能够监测植入骨折硬件的表面应变，并使用射频（RF）技术报告这些数据。这项发展计划寻求资金来进一步开展这些活动，并通过体外和动物模型建立传感器识别正常与异常骨愈合的能力。为了实现这些目标，我们提出了三个具体目标：1 -优化传感器的结构以检测应变，2 -在模拟骨折和生理环境中充分表征传感器的响应，3 -在正常和异常骨折愈合的动物模型中实现传感器，以测试我们的指导假设并进行严格的生物相容性分析。总之，这一发展方案旨在将我们的生物医学传感器从台式发展到体内环境。研究计划代表了证明该设备安全性和有效性所需的实验的逻辑进展。预计在该项目结束时，将获得足够的数据，以便提交人体临床试验申请。

DESCRIPTION (provided by applicant): The American population is treated for nearly eight million long bone fractures per year. Approximately 10% of these fractures do not heal properly. Many of these non-unions or pseudoarthroses result when there is a severe or communited (highly fragmented) condition that does not proceed through a stabilized (intramembranous ossification) healing pathway. Early detection of aberrant healing would allow for newer classes of more non-invasive revision strategies to be utilized, as well as ease the technical demands of more open revision procedures. Unfortunately, the course of aberrant fracture healing is not easily diagnosed in the early time period when standard radiographic information of the fracture site is not capable of discriminating the healing pathway. We have hypothesized that healing in the critically important early time period can be determined by monitoring of the implanted hardware mechanics. This postulation leverages the previously demonstrated phenomena whereby the soft tissue callus and newly formed bone progressively assume part of the load as healing proceeds, thus reducing the burden (and associated strain) on the implanted hardware. Thus, to address the critical need of identifying aberrant fracture healing during the early time period, we have developed a wireless, inductively-powered (no implantable power source), biocompatible micro-electromechanical sensor (bioMEMS) that is capable of monitoring the surface strain on implanted bone fracture hardware and reports these data using radio frequency (RF) technology. This development proposal seeks funding to further these activities and to establish the sensor's ability to discern normal versus aberrant bone healing using in vitro and animal models. In order to achieve these goals, we propose three specific aims: 1 - to optimize the sensor's architecture for detecting strain, 2 - to fully characterize the sensor's response in a simulated fracture and physiological environments, and 3 - to implement the sensor in an animal model of normal and aberrant fracture healing to test our guiding hypothesis and perform rigorous biocompatibility analyses. In summary, this developmental proposal seeks to evolve our bioMEMs sensor from the benchtop to the in vivo environment. The research plan represents a logical progression of experiments that are required to demonstrate the safety and efficacy of the device. It is expected that at the end of this project that sufficient data will have been obtained in order to file an application for clinical trial in human patients. PUBLIC HEALTH RELEVANCE: The American population is treated for nearly eight million long bone fractures per year and approximately 10% of these fractures do not heal properly. Unfortunately, the course of aberrant fracture healing is not easily diagnosed in the early time period when more non- invasive revision strategies could be employed. Thus, to address the critical need of identifying aberrant fracture healing during the early time period, we have developed a wireless, inductively-powered (no implantable power source) and biocompatible sensor that is capable of detecting the course of bone healing and reports these data using wireless technology.