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，但较大的节段性骨缺损更具挑战性。如果不及时治疗，这些节段性缺陷可能会导致骨不连。已知许多刺激可以增强骨再生，包括骨形态发生蛋白 - 2 (BMP-2) 和低强度脉冲超声 (LIPUS)。目前尚不清楚大节段缺损的再生过程将如何响应这两种不同模式的组合。要解决的假设是，用低强度脉冲超声和骨形态发生蛋白-2同时治疗节段性骨缺损将协同或相加地发挥作用，以增强骨再生。该假设基于我们小组最近的观察结果，即在大鼠异位骨形成模型中，LIPUS 增强了重组人 (rh)BMP-2 引发的新骨形成量。我们的目标是确定在具有良好特征的大鼠模型中，将 LIPUS 添加到 rhBMP-2 治疗节段性骨缺损是否可以加速愈合，以便开发更好的治疗方案来改善骨愈合。在目标 1 中，我们将研究节段性骨缺损对加载到可吸收胶原海绵上的不同剂量的 rhBMP-2 (1 - 205g) 的反应，以确定 rhBMP-2 的最佳剂量。将通过体内射线照片监测愈合情况。主要终点是骨量（显微计算机断层扫描和组织学）和机械强度（扭转测试）。在目标 2 中，我们将根据目标 1 中获得的信息，测试 LIPUS 在存在最佳和次优剂量的 rhBMP-2 的情况下增强修复过程的能力。主要终点与目标 1 相同。在目标 3 中，我们将确定 rhBMP-2 诱导的骨形成对最佳联合治疗形式的 LIPUS 治疗最敏感的阶段。主要终点将与目标 1 相同。由于 rhBMP-2 和 LIPUS 均已批准用于临床，因此本研究的信息可以轻松转化为临床情况。拟议的研究还可能使接受关节置换、牵引成骨和牙种植体植入等外科手术的患者受益，其中骨再生是成功结果不可或缺的一部分。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）的模型。公共健康相关性：该项目与公共健康的相关性在于，帮助骨骼修复和再生的固有能力将降低与愈合不正常和可能的不愈合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。这项研究将侧重于通过应用 FDA 批准的两种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。