Dose analysis for translating animal based vibrational force study for accelerating orthodontic tooth movement to clinic

正畸加速牙平移动物振动力研究的剂量分析 移向临床 摘要 受控差动牙齿移动(CDTM)指的是更快地移动牙齿的能力，或者 最大限度地减少牙齿的移动以保持静止(即，固定牙齿或在固位期的牙齿)。 CDTM在常见的正畸治疗中非常受欢迎，如尖牙后退、尖牙阻生、磨牙 拉长和空间关闭。成功的CDTM极大地缩短了治疗时间并减少了共同的副作用 牙根吸收和支抗丧失等影响。研究表明，间歇性振动力(IVF) 叠加正畸力可加速牙齿移动。此外，在没有正畸力的情况下， 体外受精可增强牙槽骨的骨密度。然而，目前几乎没有证据表明 刺激水平的最优选择。此外，对目标牙齿的刺激水平缺乏控制 这不可避免地导致对结果的报告不一致。拟议工作的总体目标是使 CDTM通过从成功的动物研究过渡到临床应用。计划的目标 建议的项目包括：1)确定加速正畸牙齿移动的最佳试管受精刺激水平 2)验证体外受精对牙齿强化的效果 稳定性；以及3)确定可用于扩大对较大物种的刺激水平的阈值 像狗和人类一样。我们假设：(H1)存在一个最佳的体外受精水平，可以加速 没有副作用的靶向牙齿；(H2)同样的试管受精可以强化牙齿周围的骨骼，而不会产生副作用 (3)牙周膜(PDL)中的应力可以 用作阈值，有效地将刺激水平从大鼠扩大到更大的物种，以实现 加速牙齿移动。这些假设将通过三个具体目标进行检验。目标1：确定 体外受精(OLIVF)刺激的最佳水平叠加在加速牙齿的正畸负载系统上 大鼠模型中的运动(H1)和相关的生物学反应。目的2：确定OLIVF的效果 在没有正畸力的牙齿上(H2)。目标3：扩大对包括狗在内的较大物种的刺激水平 和人类，通过在PDL中正常化应激，并在狗身上验证理论(H3)。PDL应激阈值 在这项拟议的研究中，将被用作将试管受精从大鼠扩大到狗的标准，并着眼于扩大规模 在未来的研究中取决于人类。因此，一种确保在每个人身上交付指定试管受精的新方法 诊所里的牙齿也将接受检测。这项全面的研究将为使用该技术进行临床试验铺平道路。 技术此外，相关的生物力学和生物学研究将阐明试管受精背后的机制。 这将进一步推动该领域的发展，并提供了应用该技术的方法。

Dose analysis for translating animal based vibrational force study for accelerating orthodontic tooth movement to clinic ABSTRACT Controlled Differential Tooth Movement (CDTM) refers to the ability to move teeth to be displaced faster, or to minimize the movement of teeth to be stationary (i.e., anchorage teeth or teeth during the retention phase). CDTM is highly desired in common orthodontic treatments such as canine retraction, canine impaction, molar protraction, and space closure. Successful CDTM drastically shortens treatment time and reduces common side- effects such as root resorption and anchorage loss. Studies show that an intermittent vibration force (IVF) superimposed on orthodontic force accelerates tooth movement. Further, in the absence of orthodontic force, IVF strengthens bone mineral density of the alveolar bone. However, currently there is little evidence to facilitate optimal selection of stimulation level. Furthermore, lack of control on stimulation level on the target tooth inevitably results in inconsistent reporting of outcomes. The overarching goal of the proposed work is to enable CDTM in the clinic by transitioning from successful animal studies to clinical applications. Objectives of the proposed project include: 1) identifying optimal IVF stimulation level for accelerating orthodontic tooth movement in rats as well as associated side-effects; 2) verifying effects of IVF on bone strengthening resulting in tooth stabilization; and 3) determining the threshold that can be used to scale stimulation level up for larger species like dogs and humans. We hypothesize that: (H1) there is an optimal level of IVF that accelerates movement of targeted teeth without side-effects; (H2) the same IVF can strengthen the bone surrounding the tooth without orthodontic force and reduce relapse during retention; and (H3) stress in the periodontal ligament (PDL) can be used as the threshold to effectively scale up the stimulation level from rats to larger species for achieving accelerated tooth movement. These hypotheses will be tested through three specific aims. Aim 1: Determine the optimal level of IVF (OLIVF) stimulation superimposed on an orthodontic load system that accelerates tooth movement in a rat model (H1) and the associated biological responses. Aim 2: Determine the effects of OLIVF on the tooth without orthodontic force (H2). Aim 3: Scale up stimulation level for larger species including dogs and humans, by normalizing to stress in the PDL, and validate the theory on dogs (H3). A PDL stress threshold will be used as the criterion for scaling up IVF from rats to dogs in this proposed study, with an eye toward scaling up to humans in future studies. Thus, a novel method to ensure delivery of the specified IVF on each individual tooth in the clinic will also be tested. This comprehensive study will pave the way for clinical trials using this technology. Further, associated biomechanics and biological studies will elucidate the mechanism behind IVF based CDTM, which will further advance the field as well as methods for applying this technology.