CAREER: Studying Tendon Cell Mechanobiology in the Native Tissue Environment

职业:研究天然组织环境中的肌腱细胞力学生物学

基本信息

  • 批准号:
    2142627
  • 负责人:
  • 金额:
    $ 65.47万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
    Standard Grant
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-08-01 至 2027-07-31
  • 项目状态:
    未结题

项目摘要

This Faculty Early Career Development (CAREER) grant supports research to identify how the behavior of cells within tendons is affected by tissue damage and how this leads to tendon degeneration. Previous work studied the response of tendon cells to different strains under artificial conditions. However, it is important to understand how cells response to damage inside the native tendon tissue. This is because many important interactions are lost when cells are isolated from their native environment. Also, these interactions between cells and their environment have a strong effect on cell behavior. Therefore, this project will develop novel techniques to study cell behavior in their native tissue environment. These techniques will be used to understand how tendon fatigue damage causes tendon degeneration. This information will provide the scientific foundation for developing new treatments for tendon disorders. Also, engineering students will help incorporate our results into high school biology classes. We will identify whether this improves the recruitment and retention of more women in engineering.The research goals of this CAREER project are to determine how tendon cells sense physical stimuli in the native tissue environment and to identify the role of dysfunctional cell mechanobiology in tendon degeneration. The central hypothesis is that fatigue damage alters the physical stimuli presented in situ to cells within tendon and that mechanotransduction of these altered stimuli initiates the negative cellular response leading to tendon degeneration. To test this hypothesis, the researchers will develop a live tissue explant model enabling simultaneous in situ measurement of local physical stimuli and gene expression and will identify the mechanotransduction mechanisms that drive the response of tendon cells to mechanical loading within the native tissue environment. The innovative technique of colocalizing fatigue damage (i.e., altered strains and collagen organization) with cellular gene expression will identify the specific physical stimuli that initiate tissue degeneration in the native tendon environment. Importantly, the explant model also enables the researchers to perturb mechanotransduction signaling pathways during fatigue loading and investigate their mechanistic role in inducing tendon degeneration. Beyond tendon, by investigating whether canonical mechanotransduction mechanisms observed in 2D also operate within tissue explants, this work will advance the broad understanding of how cells within fibrous soft tissues (e.g., tendon, meniscus, skin) respond to physical stimuli in the native tissue environment.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.
该学院早期职业发展(CAREER)拨款支持研究,以确定肌腱内细胞的行为如何受到组织损伤的影响以及这如何导致肌腱退化。先前的工作研究了人工条件下肌腱细胞对不同应变的反应。然而,了解细胞如何响应天然肌腱组织内的损伤非常重要。这是因为当细胞与其原生环境隔离时,许多重要的相互作用就会丢失。此外,细胞与其环境之间的相互作用对细胞行为有很大影响。因此,该项目将开发新技术来研究细胞在其天然组织环境中的行为。这些技术将用于了解肌腱疲劳损伤如何导致肌腱退化。这些信息将为开发肌腱疾病的新疗法提供科学基础。此外,工程专业的学生将帮助我们将我们的成果纳入高中生物课程。我们将确定这是否会改善工程领域更多女性的招募和保留。这个职业项目的研究目标是确定肌腱细胞如何感知天然组织环境中的物理刺激,并确定功能失调的细胞力学生物学在肌腱退化中的作用。中心假设是,疲劳损伤改变了肌腱内细胞原位呈现的物理刺激,并且这些改变的刺激的机械转导启动了导致肌腱退化的负面细胞反应。为了检验这一假设,研究人员将开发一种活体组织外植体模型,能够同时原位测量局部物理刺激和基因表达,并将确定驱动肌腱细胞对天然组织环境中的机械负荷做出反应的机械传导机制。将疲劳损伤(即改变的应变和胶原组织)与细胞基因表达共定位的创新技术将识别在天然肌腱环境中引发组织退化的特定物理刺激。重要的是,外植体模型还使研究人员能够在疲劳加载过程中扰乱机械转导信号通路,并研究它们在诱导肌腱退化中的机制作用。除了肌腱之外,通过研究在 2D 中观察到的规范机械传导机制是否也在组织外植体中起作用,这项工作将促进对纤维软组织(例如肌腱、半月板、皮肤)内的细胞如何响应天然组织环境中的物理刺激的广泛理解。该奖项反映了 NSF 的法定使命,并通过使用基金会的智力价值和更广泛的影响审查进行评估,被认为值得支持 标准。

项目成果

期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Mouse Achilles tendons exhibit collagen disorganization but minimal collagen denaturation during cyclic loading to failure
  • DOI:
    10.1016/j.jbiomech.2023.111545
  • 发表时间:
    2023-03-20
  • 期刊:
  • 影响因子:
    2.4
  • 作者:
    Pedaprolu,Krishna;Szczesny,Spencer E.
  • 通讯作者:
    Szczesny,Spencer E.
Measuring Local Tissue Strains in Tendons via Open-Source Digital Image Correlation
通过开源数字图像相关测量肌腱中的局部组织应变
  • DOI:
    10.3791/64921
  • 发表时间:
    2023
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Godshall, Stanton;Pedaprolu, Krishna;Vasti, Erica;Eskandari, Faezeh;Szczesny, Spencer E.
  • 通讯作者:
    Szczesny, Spencer E.
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Spencer Szczesny其他文献

Spencer Szczesny的其他文献

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{{ truncateString('Spencer Szczesny', 18)}}的其他基金

US-Ireland R&D Partnership: Design of Genetically Engineered Tensile Load-Bearing Soft Tissues Inspired by Embryonic Tendon Development
美国-爱尔兰 R
  • 批准号:
    2127527
  • 财政年份:
    2022
  • 资助金额:
    $ 65.47万
  • 项目类别:
    Continuing Grant

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