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Combined Use of BMP-2 and Low Intensity Pulsed Ultrasound in Bone Regeneration

BMP-2 和低强度脉冲超声在骨再生中的联合应用

基本信息

批准号：
7895830
负责人：
Amarjit Singh Virdi
金额：
$ 18.75万
依托单位：
RUSH UNIVERSITY MEDICAL CENTER
依托单位国家：
美国
项目类别：
财政年份：
2009
资助国家：
美国
起止时间：
2009-07-17 至 2012-06-30
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/7895830
关键词：
Address Affect Area Bone Morphogenetic Proteins Bone Regeneration Bone Tissue Clinical Collagen Combined Modality Therapy Defect Dental Implants Distraction Osteogenesis Dose Energy Therapy Exhibits Exploratory/Developmental Grant for Diagnostic Cancer Imaging FDA approved Fracture Fracture Healing Goals Growth Factor Healed Histology Implantation procedure Inflammatory Injury Laboratories Lateral Lead Left Length Ligaments Literature Mechanics Modality Modeling Monitor Muscle Musculoskeletal Natural regeneration Nerve Operative Surgical Procedures Orthopedics Osteogenesis Outcome Patients Phase Physiologic pulse Porifera Process Property Public Health Publishing Rattus Recovery Replacement Arthroplasty Research Risk Signal Transduction Site Specific qualifier value Stimulus Technology Tendon structure Testing Time Tissues Translating Trauma Treatment Protocols Ultrasonography United States Work X-Ray Computed Tomography base bone bone healing bone morphogenetic protein 2 clinical application design flexibility healing high risk improved in vivo meetings musculoskeletal injury novel novel strategies osteogenic public health relevance recombinant human bone morphogenetic protein-2 regenerative repaired response success

项目摘要

DESCRIPTION (provided by applicant): Fractures are a common form of musculoskeletal injury. While the inherent repair capability of bone tissue results in recovery of non-critical injuries, larger segmental bone defects are more challenging. Left untreated, these segmental defects can lead to non-unions. A number of stimuli are known to enhance bone regeneration and include bone morphogenetic protein - 2 (BMP-2) and low intensity pulsed ultrasound (LIPUS). It is presently unknown how the regenerative process in a large segmental defect will respond to a combination of these two distinct modalities. The hypothesis to be addressed is that simultaneous treatment of segmental bone defects with low intensity pulsed ultrasound and bone morphogenetic protein-2 will act synergistically or additively to enhance bone regeneration. The hypothesis is based on recent observations by our group that LIPUS enhanced the amount of new bone formation initiated by recombinant human (rh)BMP-2 in an ectopic bone formation model in the rat. Our objective is to determine if addition of LIPUS to rhBMP-2 treatment of a segmental bone defect in a well-characterized rat model accelerates healing so that better treatment protocols can be developed for improved bone healing. In Aim 1, we will study the response of segmental bone defects to varying doses of rhBMP-2 (1 - 205g) loaded on to absorbable collagen sponges in order to determine the optimum dose of rhBMP-2. Healing will be monitored by in vivo radiographs. The primary endpoints will be bone volume (micro computed tomography and histology) and mechanical strength (torsional testing). In Aim 2, we will test the ability of LIPUS to enhance the repair process in the presence of optimum and sub-optimum doses of rhBMP-2 based on information obtained in Aim 1. The primary endpoints will be the same as for Aim 1. In Aim 3, we will identify the most responsive phase(s) of rhBMP-2-induced bone formation to LIPUS treatment in the best format of combined treatment. The primary endpoints will be the same as for Aim 1. Information from this study can be readily translated to clinical situation as both rhBMP-2 and LIPUS are already approved for clinical use. The proposed research also could benefit patients undergoing surgical procedures such as joint replacement, distraction osteogenesis and dental implant placement in which bone regeneration is integral to successful outcomes. The approach proposed here might also serve as a model for the treatment of other musculoskeletal tissues (e.g., muscles, nerves, ligaments and tendons). PUBLIC HEALTH RELEVANCE: The relevance of the project to Public Health is that aiding the inherent ability of bone to repair and regenerate will reduce the risk of complications associated with subnormal healing and possible non-union. Fractures are a common form of musculoskeletal injury; there are roughly 7 million fractures per year in the United States alone. This research will focus on enhancing bone regeneration by applying a combination of two already approved FDA treatments and could be rapidly translated into clinical use.

描述（由申请人提供）：骨折是肌肉骨骼损伤的常见形式。虽然骨组织固有的修复能力可以使非严重损伤恢复，但较大节段性骨缺损更具挑战性。如果不治疗，这些节段性缺损可能导致骨不连。已知许多刺激物可增强骨再生，包括骨形态发生蛋白-2（BMP-2）和低强度脉冲超声（LIPUS）。目前尚不清楚大段缺损的再生过程将如何对这两种不同模式的组合做出反应。要解决的假设是，低强度脉冲超声和骨形态发生蛋白-2的节段性骨缺损的同时治疗将协同作用或相加，以增强骨再生。该假设是基于我们小组最近的观察，即LIPUS增强了大鼠异位骨形成模型中重组人（rh）BMP-2启动的新骨形成量。我们的目的是确定在充分表征的大鼠模型中，在rhBMP-2治疗节段性骨缺损时加入LIPUS是否加速愈合，以便开发更好的治疗方案来改善骨愈合。在目的1中，我们将研究节段性骨缺损对不同剂量的rhBMP-2（1 - 205 g）负载在可吸收胶原海绵上的反应，以确定rhBMP-2的最佳剂量。将通过体内X线片监测愈合情况。主要终点为骨体积（微型计算机断层扫描和组织学）和机械强度（扭转试验）。在目标2中，我们将根据目标1中获得的信息，在存在最佳和次佳剂量rhBMP-2的情况下，检测LIPUS增强修复过程的能力。主要终点将与目标1相同。在目标3中，我们将确定rhBMP-2诱导的骨形成对LIPUS治疗的最佳组合治疗形式的最佳反应阶段。主要终点将与目标1相同。由于rhBMP-2和LIPUS均已获批用于临床，因此本研究的信息可以很容易地转化为临床情况。拟议的研究还可以使接受关节置换、牵引成骨和牙科植入物植入等外科手术的患者受益，其中骨再生是成功结果的组成部分。这里提出的方法也可以作为治疗其他肌肉骨骼组织（例如，肌肉、神经、韧带和肌腱）。公共卫生关系：该项目与公共卫生的相关性在于，帮助骨骼修复和再生的固有能力将降低与低于正常愈合和可能的骨不连相关的并发症的风险。骨折是肌肉骨骼损伤的常见形式;仅在美国每年就有大约700万例骨折。这项研究将集中在通过应用两种已经批准的FDA治疗方法的组合来增强骨再生，并可以迅速转化为临床应用。