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Tenocyte Mechanobiology in a Fiber Composite Mimetic

纤维复合材料模拟物中的肌腱细胞力学生物学

基本信息

批准号：
1825692
负责人：
Stephanie Bryant
金额：
$ 50万
依托单位：
University of Colorado at Boulder
依托单位国家：
美国
项目类别：
Standard Grant
财政年份：
2018
资助国家：
美国
起止时间：
2018-09-01 至 2023-08-31
项目状态：
已结题

来源：
https://www.nsf.gov/awardsearch/showAward?AWD_ID=1825692&HistoricalAwards=false
关键词：
Tenocyte Mechanobiology Fiber Composite Mimetic

项目摘要

Tendons are an important tissue for musculoskeletal function -- they connect muscles to bones. They are also a very slow healing tissue, due in part to the limited blood supply and small concentration of cells within the highly fibrous structure. If tendon cells, tenocytes, are going to be stimulated to enhance tendon growth and regeneration, it is vitally important that the understanding of how these cells respond to their mechanical environment is substantially increased. This project will use a combination of computer modeling and experimental studies to investigate how tenocytes respond to complex loading normally seen in a tendon. The work will focus on the micro-level -- in order to understand how variations in the mechanical environment just around the cell relate to the cellular response. In addition to advancing knowledge that will support future work in tissue engineering of tendons and other fibrous connective tissue, this project includes several educational and outreach activities. First, the research team will integrate students from high school through graduate school in order to help them understand the importance of research in this area and of integrating experimental and computational techniques. Next, there will be an opportunity for graduate students to travel to an international collaborator's laboratory to enhance their scientific preparation. Finally, hands-on workshops will be developed to provide participants with a broader understanding of connective tissue biomechanics.The overall objectives for this project are to: (1) determine the micromechanics and the type and magnitude of the local cellular strains as a function of fiber composite properties under physiologically relevant tensile strains; (2) determine tenocyte anabolic and catabolic metabolism as a function of the type and magnitude of the local cellular strains and the typed of integrin-ligand interaction; and (3) elucidate intracellular signaling pathways based on MAP kinase signaling that are involved in integratin-mediated mechanotransduction within tenocytes. This will be done through the development of a computational model of tenocytes within a fiber-reinforced structure and the validation of this model with experimental studies using a novel hydrogel-fiber composite mimetic that captures aspects of the tendon's fiber composite mechanics.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.

肌腱是肌肉骨骼功能的重要组织--它们连接肌肉和骨骼。它们也是一种非常缓慢的愈合组织，部分原因是血液供应有限，高度纤维结构内的细胞密度很小。如果要刺激肌腱细胞来促进肌腱生长和再生，对这些细胞如何对其力学环境做出反应的了解大大增加是至关重要的。这个项目将使用计算机建模和实验研究相结合的方法来研究肌腱细胞如何对通常在肌腱中看到的复杂载荷做出反应。这项工作将集中在微观层面--以了解细胞周围机械环境的变化如何与细胞反应有关。除了促进支持肌腱和其他纤维结缔组织的组织工程未来工作的知识外，该项目还包括几项教育和外联活动。首先，研究小组将整合从高中到研究生院的学生，以帮助他们了解这一领域研究以及整合实验和计算技术的重要性。接下来，研究生将有机会前往国际合作者的实验室，以加强他们的科学准备。这个项目的总体目标是：(1)确定在生理相关拉伸应变下的微观力学以及局部细胞应变的类型和大小作为纤维复合材料性能的函数；(2)确定肌腱细胞的合成代谢和分解代谢作为局部细胞应变的类型和大小的函数以及整合素-配体相互作用的类型；以及(3)阐明基于MAP激酶信号的细胞内信号通路，该信号通路参与整合素介导腱细胞内的机械转导。这将通过开发纤维增强结构中的肌腱细胞的计算模型，并使用一种新型的水凝胶-纤维复合材料模拟物进行实验研究来验证该模型，该仿真物捕捉了肌腱的纤维复合材料机制的各个方面。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。