Matrix Mechanobiology of Ligament Repair

韧带修复的矩阵力学生物学

• 批准号: 8653276
• 负责人: Trevor Justin Lujan
• 金额: $ 22.37万
• 依托单位: BOISE STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-08-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8653276
• 关键词: Accounting; Algorithms; Applications Grants; Articular ligaments; Biology; Biomechanics; Biomedical Research; Cell Proliferation; Centers of Research Excellence; Chronic; Clinical; Clinical Trials; Collagen; Collagen Fiber; Computing Methodologies; Degenerative polyarthritis; Development; Disease; Drug Formulations; Elements; Engineering; Environment; Extracellular Matrix; Fiber; Funding; Future; Goals; Growth; Healed; Hospitals; Incidence; Inferior; Injury; Interdisciplinary Study; Intervention; Joint Instability; Joints; Lead; Ligaments; Manuals; Measures; Mechanical Stimulation; Mechanics; Mentors; Methods; Modeling; Musculoskeletal Diseases; Nature; Outcome; Process; Property; Regenerative Medicine; Research Personnel; Research Proposals; Signal Pathway; Speed; Stimulus; Structure; Technology; Testing; Tissues; United States; Validation; Visit; Work; Wound Healing; arthropathies; base; computer framework; cost; density; design; functional restoration; healing; human subject; improved; in vivo; ligament injury; mechanical behavior; repaired; research study; restoration; simulation; soft tissue; stem; therapy development; tissue repair; tool; treatment strategy

Ligament injuries cause joint instability and can lead to chronic joint disorders. The underlying cause of these functional deficits is the poor structural quality of the repaired matrix. Improvements to clinical outcomes require a mechanistic understanding ofthe physical mechanisms that instruct the restoration of matrix structure and function. The development and validation of mechanistic models would support the application and design of targeted interventions, such as soft-tissue mobilization, that apply mechanical stimuli directly to the remodeling matrix. The primary objective of this research proposal is to characterize physical mechanisms for matrix remodeling during ligament wound healing. The central hypothesis is that mechanical stimulation during wound healing can improve ligament repair by enhancing matrix composition and organization. To test this hypothesis, an experimental and computational methodology will be employed to measure and predict the structural and functional effect of mechanical stimulation on ligament reparative tissue. In Aims 1 and 2, a computational framework will be developed to predict matrix remodeling from mechanical stimulation using tissue-equivalent materials. In Aim 3, an in-vivo experiment will validate the predictive ability of this new model in a three-dimensional finite element simulation. Two potential projects stemming from this work include the design of soft tissue mobilization methods for use in human subjects (clinical trial); and the formulation of a new hypothesis on mechanotransduction mechanisms during repair. This may improve our ability to instruct signaling pathways during tissue repair, and help further our long-term goal of developing therapies for fast and full restoration of soft-tissue function after injury. As a Junior Investigator in the COBRE in Matrix Biology, I will work with my scientific mentor to complete the scientific aims and to develop a grant proposal for future R01 funding.

韧带损伤会导致关节不稳，并可能导致慢性关节疾病。这些功能不足的根本原因是修复矩阵的结构质量差。改善临床结果需要对指导基质结构和功能恢复的物理机制有一种机械理解。机械模型的开发和验证将支持直接将机械刺激直接应用于重塑矩阵的目标干预措施的应用和设计，例如软组织动员。该研究建议的主要目的是表征韧带伤口愈合过程中基质重塑的物理机制。中心假设是，在伤口愈合过程中的机械刺激可以通过增强基质组成和组织来改善韧带修复。为了检验这一假设，将采用一种实验和计算方法来测量和预测机械刺激对韧带修复组织的结构和功能效应。在目标1和2中，将开发一个计算框架，以预测使用组织等效材料从机械刺激中重塑的基质。在AIM 3中，一个体内实验将在三维有限元模拟中验证该新模型的预测能力。这项工作的两个潜在项目包括设计用于人类受试者的软组织动员方法（临床试验）；以及关于修复过程中机械转导机制的新假设的制定。这可能会提高我们在组织修复过程中指导信号通路的能力，并有助于进一步发展疗法，以便在受伤后快速，充分恢复软组织功能。作为Matrix Biology的Cobre的初级研究员，我将与我的科学导师合作完成科学目标，并为未来R01资金制定赠款建议。