NSF EAGER: Evaluation of the osteogenic benefits of low-intensity pulsed ultrasound and whole-body vibration in an in vivo rodent osseointegration model

主要研究者：Harrysson，奥拉L.提案：1441636职务：NSF EAGER：在体内啮齿动物骨整合模型中评估低强度脉冲超声和全身振动的成骨益处& 一些金属植入物被放置到骨头中，目的是永久连接。这个过程被称为骨整合（OI）。OI通常需要几周时间，快速完成OI具有优势，因为它加速了患者的康复和训练。几种策略可用于增加金属植入物的OI。它们具有外部应用的优点，并且在短时间内（约10分钟）有效。每天20分钟）。人们对这些方式的相对好处以及结合这些方式的任何潜在好处知之甚少。技术说明 本研究的目的是调查一个综合系统，以促进骨长入经皮OI植入物。这包括以下目标：（1）通过在大鼠体内的初步研究，开发和验证用于将具有优化应变和频率的受控LMHF振动传递到大鼠骨盆肢的机械驱动系统。（2）LMHF振动的相对有效性的比较（使用在目的1中开发的系统）和单独和组合的商业LIPUS，通过大鼠体内研究，（3）作为次要目的，使用双能X射线吸收测定法（DEXA）和微型计算机断层扫描（micro-CT）对骨长入和骨密度评估进行比较。（4）作为另一个次要目的，使用加速度计测量OI植入物附近的骨表面应变和植入物加速度。 提出的研究的动机是，目前一些种植体设计的OI缓慢。例如，Branemark集团植入经股骨关节炎植入物后的康复过程需要一年多的时间，并需要两次外科手术。本研究将有助于在体内啮齿动物模型中评估LMHF振动和LIPUS单独以及组合用于不同设计植入物的受益。成功完成后，拟定工作将：（1）更好地了解通过各种振动方案产生的骨表面应变，（2）开发允许局部应用LMHF振动的器械，以及（3）更好地了解LMHF振动和LIPUS对螺纹和纹理植入物骨长入的相对受益和协同作用。美国每年进行332，000例全髋关节置换术和719，000例全膝关节置换术。预计在可预见的将来，这一数字还会增加。OI牙科植入物是一个完善的医疗程序。牙种植体最常见的并发症之一是骨质疏松患者缺乏OI。 在美国，大约有170万人生活在肢体缺失的情况下，估计每年有185，000例截肢手术。到2050年，截肢人数预计将增加到360多万人。下肢截肢者通常使用承窝式假肢。这些假体有几个局限性：难以实现最佳配合，导致组织上的不良应力，可能导致压力点、软组织溃疡和神经损伤。通过OI固定的假体解决了因使用接受腔假体而导致的许多缺点，并且其应用在未来很可能会增长。安装TOP而不是接受腔假肢的患者可以过上更积极和健康的生活，更有效地为社会做出贡献。这项研究将进一步我们的战略，可能有利于个人与OI关节假体，牙种植体，透皮OI植入物的理解。通过研究促进骨长入的非侵入性、用户友好的策略，这项研究将使所有接受植入物治疗OI的患者受益。

PI: Harrysson, Ola L.Proposal: 1441636Title: NSF EAGER: Evaluation of the osteogenic benefits of low-intensity pulsed ultrasound and whole-body vibration in an in vivo rodent osseointegration modelBroader Significance & Importance Some metal implants are placed into bones with the intent of becoming permanently connected. This process is named osseointegration (OI). OI generally takes several weeks and there is an advantage in achieving rapid and complete OI because it accelerated the rehabilitation and training of patients. Several strategies may be used to increase OI of metal implants. They have the advantage to be applied externally and be effective with brief periods of exposure (approx. 20 minutes per day). Little is known about the relative benefits of these modalities and about any potential benefits of combining these modalities. Technical description The goals of this research are to investigate an integrated system to promote bone ingrowth into transdermal OI implants. This includes the following aims: (1) Development and validation of a mechanical actuation system for delivery of controlled LMHF vibration with optimized strain and frequency to the pelvic limbs of rats through a pilot in vivo study in rats, (2) The comparison of the relative effectiveness of LMHF vibration (using the system developed in Objective 1) and commercial LIPUS alone and combined, through an in vivo study in rats, (3) As a secondary objective, the comparison of bone ingrowth and bone density assessment using dual-energy X-ray absorptiometry (DEXA) and micro-computed tomography (micro-CT), (4) As another secondary objective, the comparison of bone surface strains adjacent to an OI implant and acceleration of the implant, measured using an accelerometer. The proposed research is motivated by the fact that OI is slow with some current implant designs. For example, the rehabilitation process after placement of a transfemoral OI implant by the Branemark group takes more than one year and requires two surgical procedures. This research will help evaluate the benefits of LMHF vibration and LIPUS alone and combined for implants with different designs in an in vivo rodent model. Upon successful completion, the proposed work will: (1) yield a better understanding of the bone surface strains generated through various vibration protocols, (2) lead to the development of a device allowing the local application of LMHF vibration, and (3) yield a better understanding of the relative benefit and synergy of LMHF vibration and LIPUS on bone ingrowth of threaded and textures implants. 332,000 total hip replacement and 719,000 total knee replacements are performed annually in the United States. This number is anticipated to grow in the foreseeable future. OI dental implants are a well-established medical procedure. One of the most common complications of dental implants is the lack of OI in patients with preexisting osteoporosis. Approximately 1.7 million people live with a missing limb in the United States and an estimated 185,000 amputations are performed each year. The number of individuals experiencing amputation is predicted to increase to more than 3.6 million by 2050. Lower limb amputees commonly use socket-type prostheses. These prostheses have several limitations: optimal fit is difficult to achieve causing undesirable stresses on tissues that can lead to pressure points, soft tissue sores, and nerve damage. Prostheses fixed by OI address many of the shortcomings resulting from the use of socket prostheses and their applications will most likely grow in the future. Patients fitted with a TOP instead of a socket prosthetics can live more active and healthy lives and more efficiently contribute to society. This research will further our understanding of strategies that may benefit individuals with OI joint prostheses, with dental implants, and with transdermal OI implants. By investigating non-invasive, user-friendly strategies that promote bone ingrowth, this research will benefit all patients receiving implants with the intent of OI.