Extracorporeal Shock Wave-Stimulated Periosteum for Bone Reconstruction

体外冲击波刺激骨膜进行骨重建

基本信息

  • 批准号:
    8088995
  • 负责人:
  • 金额:
    --
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2011
  • 资助国家:
    美国
  • 起止时间:
    2011-03-01 至 2015-02-28
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): There are 4 specific aims for this study. Specific Aim #1 is to determine the effects of extracorporeal shock waves (ESWs) on the proliferation of osteogenic cells in the periosteum of the tibia and edentulous mandible of the same animals, by conducting a dose-response experiment. Three energy densities will be employed (0, 0.15, and 0.45 mJ/mm2; a one-time application of 3,000 shocks for each energy density), and the results compared after 2, 4, and 8 days. The outcome variables will be selected cell counts and periosteum thickness measurement from histomorphometry employing immunohistochemistry, and osteogenic cell culture assay. Our objective is to find the dose (0.15 vs 0.45 mJ/mm2) and time post-treatment that yields the greatest number of osteogenic cells prior to the formation of bone. The goal is to be able to elevate or harvest the proliferating cambium layer of cells; the presence of bony trabeculae would interfere with the harvest of the cells. Our initial goal, in this proposal, is to harvest the osteogenic cells; future studies may be directed toward harvesting the cancellous bone that forms in the ESW-stimulated periosteum. Specific Aim #2 is to determine the effects of ESWs on the osteogenic cells in the marrow of the same tibial and mandibular samples employed in Specific Aim #1. We have already found in prior work that ESWs induce changes in the marrow. We have been informed by a pathologist that the changes are consistent with those that would be expected to be reversible, and of no adverse clinical consequence. We would like to determine if the ESW-stimulated marrow contains a greater percentage of mesenchymal stem cells (MSCs; i.e., marrow stromal cells, or osteoprogenitor cells). We will make this determination by assaying the osteogenic potential of the marrow in the cell culture assay. If we find that ESWs do, in fact, stimulate osteogenic cellular activity in the marrow, this will be investigated in future studies. The findings could be of value in developing a simple, non-invasive procedure for enhancing an alternative autologous cell source (i.e., marrow) for bone reconstruction procedures. Specific Aim #3 is to determine the effects of ESW-stimulated periosteum on bone regeneration in porous calcium phosphate (CaP) blocks in defects in the mandible. The ESW dose that yields the greatest number of osteogenic cells in Specific Aim #1 will be applied to the periosteum of the edentulous premolar region of goats. After the prescribed period post-ESW, the periosteum will be elevated and a porous CaP block containing 2 threaded titanium implants placed into the surgically prepared site. The elevated periosteum will then be applied to the surface of the block. In another group of animals the ESW-stimulated periosteum of the tibia will be harvested as a free autologous graft to be applied to the CaP block. In Specific Aim #4, recombinant human (rh) PDGF-BB will be incorporated into the CaP block before it is implanted into the defect and covered with the ESW-stimulated periosteum as in Specific Aim #3. PUBLIC HEALTH RELEVANCE: Mandibular, maxillofacial, and craniofacial injuries to bone are devastating and have two features which make them especially challenging to treat: the absence of sufficient pools of osteoprogenitor cells in the vicinity of the defect; the necessity to provide contour to the bone and have that contour maintained for the long term. The system which we propose includes 3 "devices": a shock wave apparatus; a porous bone mineral scaffold; and a bone growth factor. The devices are currently approved by the Food and Drug Administration (FDA) individually for other applications. The key feature of the bone reconstruction system is the use of extracorporeal (non-invasive) shock waves to stimulate the proliferation of osteoprogenitor cells a few days prior to the bone reconstruction procedure.
描述(由申请人提供): 本研究有四个具体目标。 具体目标#1是通过进行剂量反应实验,确定体外冲击波(ESW)对相同动物胫骨和无牙下颌骨骨膜中成骨细胞增殖的影响。将采用三种能量密度(0、0.15和0.45 mJ/mm 2;每种能量密度一次性施加3,000次冲击),并在2、4和8天后比较结果。结果变量将是采用免疫组织化学和成骨细胞培养测定的组织形态计量学中选定的细胞计数和骨膜厚度测量值。我们的目标是找到在骨形成之前产生最大数量的成骨细胞的治疗后剂量(0.15与0.45 mJ/mm 2)和时间。目标是能够提升或收获细胞的增殖形成层;骨小梁的存在会干扰细胞的收获。我们的初步目标,在这个建议中,是收获成骨细胞,未来的研究可能会针对收获松质骨,在ESW刺激骨膜形成。 具体目标#2是确定ESW对具体目标#1中使用的相同胫骨和下颌骨样本骨髓中的成骨细胞的影响。我们已经在先前的工作中发现,ESW诱导骨髓的变化。病理学家告知我们,这些变化与预期可逆的变化一致,并且没有不良临床后果。我们想确定ESW刺激的骨髓是否含有更大百分比的间充质干细胞(MSC;即,骨髓基质细胞或骨祖细胞)。我们将通过在细胞培养试验中测定骨髓的成骨潜力来确定这一点。如果我们发现ESW确实刺激骨髓中的成骨细胞活性,这将在未来的研究中进行调查。这些发现对于开发一种简单的、非侵入性的方法来增强替代的自体细胞来源(即,骨髓)用于骨重建手术。 具体目标#3是确定ESW刺激的骨膜对下颌骨缺损中多孔磷酸钙(CaP)块中骨再生的影响。将在特定目标#1中产生最大数量成骨细胞的ESW剂量应用于山羊无牙前磨牙区域的骨膜。在ESW后规定的时间段后,将骨膜抬高,并将含有2个螺纹钛植入物的多孔CaP块置于手术准备部位。然后将升高的骨膜应用于块的表面。在另一组动物中,将采集ESW刺激的胫骨骨膜作为游离自体移植物,应用于CaP块。 在具体目标#4中,将重组人(rh)PDGF-BB掺入CaP块中,然后将其植入缺损处,并用ESW刺激的骨膜覆盖,如具体目标#3所述。 公共卫生相关性: 下颌骨、颌面部和颅面骨损伤是毁灭性的,并且具有两个特征,这使得它们特别具有治疗挑战性:在缺损附近缺乏足够的骨祖细胞池;必须为骨提供轮廓并使该轮廓长期保持。我们提出的系统包括3个“装置”:冲击波装置;多孔骨矿物质支架;和骨生长因子。这些设备目前已获得美国食品和药物管理局(FDA)的批准,可单独用于其他应用。骨重建系统的关键特征是在骨重建手术前几天使用体外(非侵入性)冲击波刺激骨祖细胞增殖。

项目成果

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Myron Spector其他文献

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{{ truncateString('Myron Spector', 18)}}的其他基金

Shock Waves and Injectable Gelatin Matrix for Cartilage Repair
用于软骨修复的冲击波和可注射明胶基质
  • 批准号:
    10292916
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
Shock Waves and Injectable Gelatin Matrix for Cartilage Repair
用于软骨修复的冲击波和可注射明胶基质
  • 批准号:
    9188891
  • 财政年份:
    2017
  • 资助金额:
    --
  • 项目类别:
Extracorporeal Shock Wave-Stimulated Periosteum for Bone Reconstruction
体外冲击波刺激骨膜进行骨重建
  • 批准号:
    8840072
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
Extracorporeal Shock Wave-Stimulated Periosteum for Bone Reconstruction
体外冲击波刺激骨膜进行骨重建
  • 批准号:
    8838173
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
Extracorporeal Shock Wave-Stimulated Periosteum for Bone Reconstruction
体外冲击波刺激骨膜进行骨重建
  • 批准号:
    8240900
  • 财政年份:
    2011
  • 资助金额:
    --
  • 项目类别:
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