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 me...