Collaborative Research: Wireless-Powered Implantable Bone Intramedullary Fluid Modulator for the Treatment of Osteoporosis and Fracture Repair

合作研究：用于治疗骨质疏松症和骨折修复的无线植入式骨髓内液调节器

• 批准号: 1710824
• 负责人: Jeong Bong Lee
• 金额: $ 25万
• 依托单位: University of Texas at Dallas
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-07-01 至 2021-12-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1710824&HistoricalAwards=false
• 关键词: Collaborative; Research; Wireless; Powered; Implantable

Numerous previous studies demonstrated that modulation of flow inside bone marrow enhances bone growth. However, to date there are no reports on a miniature device that can be implanted inside of bone. The goals of the proposed work are to design and fabricate a wireless, battery-less, implantable miniature device to treat low bone mass and fracture repair. The project will provide ample research opportunities for graduate/undergraduate students at the University of Texas at Dallas and the University of Texas at Arlington. The program will also have a strong impact on diversity. Both institutions will actively reach out to underrepresented minority students through the established programs. This project is anticipated to make an impact in both research and educational aspects of North Texas biomedical, semiconductor, and nanotech industries, by developing new technologies with high commercial potential and also by supplying well-trained scientists and engineers. This project is anticipated to have immense impact on health care and research related to bone disease.The research goals of the proposed work are to design and fabricate a wireless, battery-less, implantable fluid modulator to treat low bone mass and fracture repair. Numerous in vitro studies eliciting bone formation and inhibiting bone resorption via intramedullary fluid flow modulation have been conducted. In vivo studies modulating intramedullary fluid flow are rare due to methodological difficulties; i.e., the ability to modulate intramedullary fluid flow without concomitant mechanical strain on the skeleton. To date there are no reports in the literature that utilizes compact, wireless and chronically implantable devices for in vivo bone intramedullary fluid modulation. The purposes of this proposal are to 1) develop a wireless, implantable bone intramedullary fluid modulator which can reliably modulate bone intramedullary fluid flow by external magnetic field, 2) also utilize the wireless fluid modulator to detect real-time bone intramedullary pressure in a battery-less, wireless manner, and 3) determine whether the wireless fluid modulator will stimulate bone formation and augment bone mass in young and old rats. The fluid modulator has a wireless passive pressure sensor for real-time intramedullary fluid pressure measurement and micro magnetic agitators for on-demand wireless intramedullary fluid flow modulation. The passive pressure sensor is designed to have a parallel plate capacitor with one electrode on a membrane which deflects in response to surrounding intramedullary fluid pressure. The pressure sensor will be inductively coupled to an external coil outside of a body using radio frequency (e.g., 200 MHz). The change in intramedullary fluid pressure will be read by the external coil as phase dip frequency shifts. Magnetic agitators will be designed to have optimal fluid modulation inside the limited space of the femoral intramedullary cavity (e.g., approximately 13 mm in length, 1.7 mm in diameter for 6 month old rats). Microfabrication techniques will be utilized to electroplate permalloy or permanent magnet to get micro magnetic agitators. The proposed wireless fluid modulator will be implanted inside the intramedullary cavity of rats using a conventional syringe (e.g., 16G needle). Changes in bone mass as a result of alterations in intramedullary fluid flow and pressure in the absence of mechanical loading will be studied. Following chronic implantation and periodic activation of the fluid modulator for 30 days, bone mass and bone cellular activity will be evaluated and compared between young and old rats. The proposed wireless fluid modulator may be groundbreaking in its ability to non-pharmacologically stimulate bone growth and fracture healing and have great potential in a variety of clinical and veterinarian applications.

许多先前的研究表明，骨髓内流动的调节促进骨生长。然而，到目前为止，还没有关于可以植入骨内的微型器械的报道。这项工作的目标是设计和制造一种无线的、无电池的、可植入的微型设备来治疗低骨量和骨折修复。该项目将为德克萨斯大学达拉斯分校和德克萨斯大学阿灵顿分校的研究生/本科生提供充足的研究机会。该计划还将对多样性产生重大影响。这两个机构将通过既定的计划积极接触代表性不足的少数民族学生。该项目预计将通过开发具有高商业潜力的新技术以及提供训练有素的科学家和工程师，在北德克萨斯州生物医学，半导体和纳米技术行业的研究和教育方面产生影响。本研究的目的是设计并制作一种无线、无电池、可植入式的流体调制器，用于治疗低骨量和骨折修复。已经进行了许多体外研究，通过髓内液流动调节诱导骨形成和抑制骨吸收。由于方法上的困难，调节髓内液流动的体内研究很少;即，调节髓内流体流动而不伴随骨骼上的机械应变的能力。到目前为止，文献中还没有使用紧凑型、无线和长期植入式器械进行体内骨髓内液调节的报告。本发明的目的是：1）开发一种无线、可植入的骨髓内流体调制器，其可以通过外部磁场可靠地调制骨髓内流体流动，2）还利用无线流体调制器以无电池、无线的方式实时检测骨髓内压力，和3）确定无线流体调节器是否将刺激年轻和年老大鼠的骨形成和增加骨量。流体调节器具有用于实时髓内流体压力测量的无线无源压力传感器和用于按需无线髓内流体流量调节的微型磁性搅拌器。无源压力传感器被设计为具有平行板电容器，其中一个电极在膜上，该膜响应于周围髓内流体压力而偏转。压力传感器将使用射频（例如，200 MHz）。髓内流体压力的变化将被外部线圈读取为相位下降频率偏移。磁性搅拌器将被设计为在股骨髓腔的有限空间内具有最佳的流体调节（例如，对于6个月大的大鼠，长度约为13 mm，直径为1.7 mm）。利用微细加工技术，将坡莫合金或永磁体镶嵌在一起，制成微型磁力搅拌器。所提出的无线流体调制器将使用常规注射器（例如，16 G针头）。将研究在没有机械负荷的情况下，由于髓内液流量和压力的改变而导致的骨量变化。在长期植入和定期激活液体调节剂30天后，将评价骨量和骨细胞活性，并在年轻和老年大鼠之间进行比较。所提出的无线流体调制器在其非骨刺激骨生长和骨折愈合的能力方面可能是开创性的，并且在各种临床和兽医应用中具有巨大的潜力。

项目成果

An Implanted Magnetic Microfluidic Pump for In Vivo Bone Remodeling Applications

• DOI: 10.3390/mi11030300
• 发表时间: 2020-03-01
• 期刊: MICROMACHINES
• 影响因子: 3.4
• 作者: Chen, Ziyu;Noh, Sunggi;Lee, Jeong-Bong
• 通讯作者: Lee, Jeong-Bong

Axially-Anisotropic Hierarchical Grating 2D Guided-Mode Resonance Strain-Sensor

轴向各向异性分层光栅二维导模谐振应变传感器

• DOI: 10.3390/s19235223
• 发表时间: 2019
• 期刊: Sensors
• 影响因子: 3.9
• 作者: Babu, Sachin;Lee, Jeong-Bong
• 通讯作者: Lee, Jeong-Bong

Implanted Wireless Intramedullary Fluid Modulator for Bone Density Augmentation

用于增加骨密度的植入式无线髓内流体调节器

• DOI: 10.1109/mems46641.2020.9056219
• 发表时间: 2020
• 期刊: 2020 IEEE 33rd International Conference on Micro Electro Mechanical Systems (MEMS
• 作者: Chen, Ziyu;Noh, Sunggi;Prisby, Rhonda D.;Lee, Jeong-Bong
• 通讯作者: Lee, Jeong-Bong