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

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装置的报道。这项工作的目标是设计和制造一种无线、无电池、可植入的微型设备，用于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。这两所大学都将通过现有的项目积极接触被忽视的少数族裔学生。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，对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。预计该项目将对与骨病有关的卫生保健和研究产生巨大影响。本课题的研究目标是设计和制造一种无线、无电池、可植入的液体调制器，用于治疗低骨量和骨折修复。已经进行了许多体外研究，通过髓内液体流动调节诱导骨形成和抑制骨吸收。由于方法上的困难，调节髓内液体流动的体内研究很少；即，调节髓内流体流动而不伴随骨骼的机械应变的能力。到目前为止，文献中还没有使用紧凑、无线和长期植入式装置进行体内骨髓内液调节的报道。本研究的目的是：1)开发一种无线、可植入的骨髓内液体调制器，它可以通过外磁场可靠地调节骨髓内液体的流动；2)利用无线液体调制器以无电池、无线的方式实时检测骨髓内压力；3)确定无线液体调制器是否会刺激幼龄和老年大鼠的骨形成和增加骨量。该流体调制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制的微磁搅拌器。无源压力传感器被设计成有一个平行板电容器，一个电极在膜上，响应周围的髓内流体压力而偏转。压力传感器将使用射频（例如，200mhz）电感耦合到身体外部的外部线圈上。外部线圈将读取髓内流体压力的变化，作为相位倾斜频率的移动。磁性搅拌器将被设计成在股髓内腔有限的空间内具有最佳的流体调节（例如，6个月大的大鼠长约13毫米，直径约1.7毫米）。微加工技术将被用于电镀永磁体或永合金以得到微磁搅拌器。所提出的无线流体调制器将使用常规注射器（例如16G针）植入大鼠的髓腔内。在没有机械负荷的情况下，骨量的变化是由于髓内流体流动和压力的改变而引起的。在慢性植入和周期性激活液体调节剂30天后，将评估和比较年轻和年老大鼠的骨量和骨细胞活性。所提出的无线流体调节剂在其非药物刺激骨骼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。

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.