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

PI：Harrysson，Ola L.Proposal：1441636标题：NSF ENGER：在活体啮齿动物骨整合模型中评估低强度脉冲超声波和全身振动的成骨益处Broader重要性和重要性一些金属植入物被放置到骨骼中，目的是成为永久连接的意图。这个过程被称为骨整合(OI)。OI一般需要几周的时间，实现快速和完整的OI具有优势，因为它加速了患者的康复和训练。可以使用几种策略来增加金属植入物的OI。它们的优势是可以在外部使用，并在短暂的暴露时间内有效(约每天20分钟)。人们对这些模式的相对好处以及合并这些模式的任何潜在好处知之甚少。技术描述本研究的目标是研究一种促进经皮OI植入物的骨生长的集成系统。这包括以下目的：(1)通过大鼠体内试验，开发和验证用于将具有最佳应变和频率的受控LMHF振动传递到大鼠骨盆四肢的机械驱动系统，(2)通过大鼠体内研究，比较LMHF振动(使用在目标1中开发的系统)和商业LIPUS单独和组合的相对有效性，(3)作为次要目标，使用双能X射线吸收测量仪(DEXA)和微计算机断层扫描(Micro-CT)比较骨生长和骨密度评估，(4)作为另一个次要目标，使用加速度计测量OI种植体附近的骨表面应变和种植体的加速度。这项拟议的研究是由于目前一些种植体设计的OI速度较慢这一事实。例如，Branemark小组放置经股动脉OI植入物后的康复过程需要一年多的时间，需要两次手术。这项研究将有助于评估LMHF振动和LIPUS单独以及联合使用不同设计的植入物在活体啮齿动物模型中的益处。成功完成后，拟议的工作将：(1)更好地了解通过各种振动方案产生的骨表面应变，(2)开发一种允许局部应用LMHF振动的设备，以及(3)更好地了解LMHF振动和LIPUS在螺纹和纹理种植体的骨植入方面的相对优势和协同作用。在美国，每年进行33.2万次全髋关节置换和71.9万次全膝关节置换。在可预见的未来，这一数字预计还会增长。OI牙科植入物是一种成熟的医疗程序。牙种植体最常见的并发症之一是先前存在的骨质疏松症患者缺乏OI。在美国，大约有170万人生活在失去肢体的情况下，估计每年有18.5万人接受截肢手术。预计到2050年，接受截肢的人数将增加到360万人以上。截肢者通常使用插座式假肢。这些假体有几个局限性：很难达到最佳配合，对组织造成不必要的压力，可能导致压力点、软组织溃疡和神经损伤。由OI固定的假体解决了使用插座假体所产生的许多缺点，它们的应用在未来很可能会增长。患者佩戴上盖而不是插座假体可以过上更积极、更健康的生活，并更有效地为社会做出贡献。这项研究将进一步加深我们对OI关节假体、牙科植入物和透皮OI植入物可能受益的策略的理解。通过研究非侵入性、用户友好的促进骨生长的策略，这项研究将使所有接受OI意图的植入物的患者受益。

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.