Suture Mechanobiology and the Vasculature: A New Approach to Midfacial Hypoplasia

缝合机械生物学和脉管系统:面中部发育不全的新方法

基本信息

  • 批准号:
    9181214
  • 负责人:
  • 金额:
    $ 23.18万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-07-01 至 2018-06-30
  • 项目状态:
    已结题

项目摘要

Midfacial hypoplasia is a growth deficiency that can lead to severe deformity with impairment of feeding and breathing. Current treatments include drastic surgeries that reposition bones but do not promote growth. This project assesses the potential of a less invasive mechanotherapeutic strategy for preventing the early fusion of hypoplastic midfacial sutures. Cyclic loading is anabolic for sutures. As a working hypothesis, we propose that cyclic loading preserves patency by promoting the proliferation of sutural cells, and that in the central zone these cells are inhibited from becoming osteoprogenitors. The proposed mechanism by which this occurs is that the central zone of the suture becomes hypoxic as cyclic loading disrupts blood flow. Hypoxia then leads to mesenchymal proliferation, angiogenesis, and matrix remodeling; these events inhibit cells from osteodifferentiation until they move out of the central zone into the bone-forming zones. In this way mechanotherapy would both preserve sutural patency and promote bone growth. The Aims of the project will test the clinical validity of the cyclic loading concept, the working hypothesis, and the proposed vascular mechanism. It will serve as proof of principle for future investigations of molecular mechanisms and the development of new treatment modalities. Minipigs are similar to humans in craniofacial physiology, and their sutural mechanics are well documented. We will employ a unique minipig breed with severe midfacial hypoplasia related to hypoplastic, early fusing facial sutures. Cyclic or sham loads will be applied to sutures and the resulting strains measured using strain gages. Specific Aim 1 will test whether the hypoplastic sutures increase their growth in response to the treatment. Specific Aim 2 will test the working hypothesis by determining sutural proliferation/apoptotic rates and establishing whether osteoprogenitors are downregulated in the central zone. Specific Aim 3 will test the predictions of the vascular mechanism that loading will increase vascularity and disorganize the sutural ligament. This research will advance our understanding of the biological regulation of suture patency and elucidate the pathogenesis of midfacial hypoplasia. If the concept, working hypothesis and/or the vascular mechanism are supported by the findings, our long-term goal will be to develop mechanical and pharmacological therapies for this serious disorder.
面中部发育不全是一种生长缺陷,可导致严重畸形,并伴有进食障碍, 呼吸了目前的治疗方法包括剧烈的手术,重新定位骨骼,但不能促进生长。这 该项目评估了一种微创机制策略预防早期融合的潜力, 面中缝发育不全循环负载是缝线的合成代谢。作为一个工作假设,我们建议 循环负荷通过促进缝合细胞的增殖来保持通畅性, 这些细胞被抑制成为骨祖细胞。发生这种情况的拟议机制是 缝合线的中心区域变得缺氧,因为循环负荷破坏了血流。缺氧会导致 间充质增殖,血管生成和基质重塑;这些事件抑制细胞从 骨分化,直到它们从中心区移动到骨形成区。以这种方式 机械疗法既能保持缝合通畅又能促进骨生长。该项目的目标将 测试循环载荷概念、工作假设和拟定血管的临床有效性 机制它将作为未来分子机制研究的原则证明, 开发新的治疗模式。小型猪在颅面生理学上与人类相似, 缝合力学是有据可查的。我们将采用一种独特的迷你猪品种, 与发育不全有关的发育不全,早期融合的面部缝合。将施加循环或假载荷, 缝线和使用应变计测量的所得应变。具体目标1将测试 发育不全的缝合增加了它们对治疗的反应。具体目标2将测试工作 通过确定缝增殖/凋亡率并确定骨祖细胞是否 在中心区域下调。具体目标3将测试血管机制的预测, 负荷将增加血管分布并破坏缝合韧带。这项研究将推动我们的 了解缝线通畅的生物学调节,阐明面中部的发病机制, 发育不全如果发现支持概念、工作假设和/或血管机制, 我们的长期目标将是为这种严重的疾病开发机械和药物疗法。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

SUSAN W HERRING其他文献

SUSAN W HERRING的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('SUSAN W HERRING', 18)}}的其他基金

Suture Mechanobiology and the Vasculature: A New Approach to Midfacial Hypoplasia
缝合机械生物学和脉管系统:面中部发育不全的新方法
  • 批准号:
    9294987
  • 财政年份:
    2016
  • 资助金额:
    $ 23.18万
  • 项目类别:
Comprehensive Training in Inter-Disciplinary Oral Health Research
跨学科口腔健康研究综合培训
  • 批准号:
    9356801
  • 财政年份:
    2012
  • 资助金额:
    $ 23.18万
  • 项目类别:
Botulinum toxin in muscles of mastication
咀嚼肌中的肉毒杆菌毒素
  • 批准号:
    7583606
  • 财政年份:
    2008
  • 资助金额:
    $ 23.18万
  • 项目类别:
Botulinum toxin in muscles of mastication
咀嚼肌中的肉毒杆菌毒素
  • 批准号:
    7694343
  • 财政年份:
    2008
  • 资助金额:
    $ 23.18万
  • 项目类别:
Botulinum toxin in muscles of mastication
咀嚼肌中的肉毒杆菌毒素
  • 批准号:
    8103034
  • 财政年份:
    2008
  • 资助金额:
    $ 23.18万
  • 项目类别:
Botulinum toxin in muscles of mastication
咀嚼肌中的肉毒杆菌毒素
  • 批准号:
    8291109
  • 财政年份:
    2008
  • 资助金额:
    $ 23.18万
  • 项目类别:
Botulinum toxin in muscles of mastication
咀嚼肌中的肉毒杆菌毒素
  • 批准号:
    7872827
  • 财政年份:
    2008
  • 资助金额:
    $ 23.18万
  • 项目类别:
MECHANICAL ENVIRONMENT IN MANDIBULAR DISTRACTION
下颌牵引的机械环境
  • 批准号:
    6415875
  • 财政年份:
    2002
  • 资助金额:
    $ 23.18万
  • 项目类别:
MECHANICAL ENVIRONMENT IN MANDIBULAR DISTRACTION
下颌牵引的机械环境
  • 批准号:
    6620346
  • 财政年份:
    2002
  • 资助金额:
    $ 23.18万
  • 项目类别:
MECHANICAL ENVIRONMENT IN MANDIBULAR DISTRACTION
下颌牵引的机械环境
  • 批准号:
    7002332
  • 财政年份:
    2002
  • 资助金额:
    $ 23.18万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Fellowship
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Research Grant
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 23.18万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了