Cellular and Mechanical Mechanisms Regulating Mandibular Distraction Osteogenesis

调节下颌牵张成骨的细胞和机械机制

基本信息

  • 批准号:
    9889815
  • 负责人:
  • 金额:
    $ 37.52万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2017
  • 资助国家:
    美国
  • 起止时间:
    2017-04-01 至 2022-03-31
  • 项目状态:
    已结题

项目摘要

Project Summary Craniofacial skeletal deficiencies involving the mandible, midface, and cranial vault result in a wide range of disabilities including severe airway compromise, malocclusion, inadequate corneal protection, and neurological impairment. Secondary to trauma, tumor resection, or developmental anomalies, these deformities represent a significant reconstructive challenge and account for over $1 billion in annual health care expenditures. While surgical techniques integrating conventional osteotomies with autogenous bone and/or synthetic graft materials can be successful, limitations in donor site morbidity, biocompatibility, and osteoconductivity still remain. As an alternative approach, distraction osteogenesis (DO) offers the ability to promote endogenous bone formation across a mechanically controlled environment, providing anatomical and functional replacement of deficient tissue. The application of DO to the craniofacial skeleton has revolutionized the treatment of many congenital and acquired defects, and for many patients with mandibular deficiency associated with Pierre-Robin sequence, Treacher Collins syndrome, and craniofacial microsomia, distraction osteogenesis has become the treatment choice. We have developed a novel model of mouse mandibular distraction which allows for lineage tracing of cellular contribution to the regenerate and genetic dissection of biomechanical force transduction regulating cell differentiation during guided bone formation. Findings from this proposal will deepen our knowledge of how progenitor cells localize to the regenerate and enhance our understanding of craniofacial distraction. The identification of the cellular source within the DO regenerate, the timeline for progenitor cell response, and determination of how these cells transduce physical stimuli to enact a regenerative response may all facilitate development of improved distraction protocols. Findings from this proposal may provide new and effective strategies for reconstruction of the craniofacial skeleton.
项目摘要 涉及下颌骨、面中部和颅穹窿的颅面骨骼缺陷导致广泛的残疾,包括严重的气道损害、咬合不正、角膜保护不足和神经功能障碍。继发于创伤、肿瘤切除或发育异常,这些畸形是一个重大的重建挑战,每年的医疗保健支出超过10亿美元。虽然将传统截骨术与自体骨和/或合成移植物材料相结合的手术技术可以取得成功,但供体部位发病率、生物相容性和骨传导性方面的局限性仍然存在。作为一种替代方法,牵张成骨(DO)提供了在机械控制环境中促进内源性骨形成的能力,为有缺陷的组织提供解剖和功能替代。DO在颅面骨骼的应用彻底改变了许多先天性和后天性缺陷的治疗,对于许多与Pierre-Robin序列、Treacher柯林斯综合征和颅面矮小症相关的下颌骨缺损患者,牵引成骨已成为治疗选择。我们开发了一种新型的小鼠下颌骨牵拉模型,可以追踪细胞对再生的贡献,并对引导骨形成过程中调节细胞分化的生物力学力传导进行遗传解剖。这项研究的发现将加深我们对祖细胞如何定位于再生的认识,并增强我们对颅面牵引的理解。DO再生内的细胞源的鉴定、祖细胞响应的时间轴以及这些细胞如何抵抗物理刺激以产生再生响应的确定都可以促进改进的牵引方案的开发。本研究结果可能为颅面骨骼重建提供新的有效策略。

项目成果

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MICHAEL T LONGAKER其他文献

MICHAEL T LONGAKER的其他文献

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{{ truncateString('MICHAEL T LONGAKER', 18)}}的其他基金

Defining the role of mechanoresponsive adipocyte-to-fibroblast transition in wound fibrosis.
定义机械反应性脂肪细胞向成纤维细胞转变在伤口纤维化中的作用。
  • 批准号:
    10654464
  • 财政年份:
    2023
  • 资助金额:
    $ 37.52万
  • 项目类别:
Mechanoresponsive Engrailed-1-negative fibroblasts activate Engrailed-1 to promote fibrosis in wound healing
机械反应性 Engrailed-1 阴性成纤维细胞激活 Engrailed-1 以促进伤口愈合中的纤维化
  • 批准号:
    10550197
  • 财政年份:
    2020
  • 资助金额:
    $ 37.52万
  • 项目类别:
Identifying the human skeletal stem cell.
识别人类骨骼干细胞。
  • 批准号:
    10210253
  • 财政年份:
    2018
  • 资助金额:
    $ 37.52万
  • 项目类别:
Identifying the human skeletal stem cell.
识别人类骨骼干细胞。
  • 批准号:
    9975006
  • 财政年份:
    2018
  • 资助金额:
    $ 37.52万
  • 项目类别:
Identifying the human skeletal stem cell.
识别人类骨骼干细胞。
  • 批准号:
    9756366
  • 财政年份:
    2018
  • 资助金额:
    $ 37.52万
  • 项目类别:
Irradiated head and neck cancer soft tissue reconstruction by fat transfer.
通过脂肪移植进行辐照头颈癌软组织重建。
  • 批准号:
    10403603
  • 财政年份:
    2018
  • 资助金额:
    $ 37.52万
  • 项目类别:
Identifying the human skeletal stem cell.
识别人类骨骼干细胞。
  • 批准号:
    10453593
  • 财政年份:
    2018
  • 资助金额:
    $ 37.52万
  • 项目类别:
Cellular and Mechanical Mechanisms Regulating Mandibular Distraction Osteogenesis
调节下颌牵张成骨的细胞和机械机制
  • 批准号:
    9281376
  • 财政年份:
    2017
  • 资助金额:
    $ 37.52万
  • 项目类别:
Cellular and Mechanical Mechanisms Regulating Mandibular Distraction Osteogenesis
调节下颌牵张成骨的细胞和机械机制
  • 批准号:
    9463620
  • 财政年份:
    2017
  • 资助金额:
    $ 37.52万
  • 项目类别:
Enhancing Bcl-2 Expression for Bone Regeneration.
增强 Bcl-2 表达促进骨再生。
  • 批准号:
    8676512
  • 财政年份:
    2014
  • 资助金额:
    $ 37.52万
  • 项目类别:

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