Mechanical Factors and Cellular Responsiveness in Fracture Repair

骨折修复中的机械因素和细胞反应性

• 批准号: 7196574
• 负责人: Steven A Goldstein
• 金额: $ 29.29万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2007
• 资助国家: 美国
• 起止时间: 2007-06-15 至 2012-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7196574
• 关键词: Angiogenic Factor; Biological Factors; Biomechanics; Bone Regeneration; Cell Proliferation; Cells; Complex; Development; Devices; Event; Extracellular Matrix; Fracture; Fracture Fixation; Fracture Healing; Gene Expression; Growth Factor Overexpression; Healed; Hormones; In Situ; Lead; Mechanical Stimulation; Mechanics; Mediating; Mesenchymal; Modeling; Molecular; Natural regeneration; Nutritional Support; Phase; Population; Process; Purpose; Rate; Rattus; Research Project Grants; Role; Signal Transduction; Site; Spatial Distribution; Stem cells; Stimulus; Time; Tissue Differentiation; Tissue Engineering; Tissues; Vascular blood supply; Work; bone; bone morphogenetic protein 2; cell type; healing; health care delivery; improved; insight; lost work time; neovascularization; repaired; response; sensor

DESCRIPTION (provided by applicant): Recent work has suggested that physical forces transmitted to the site of bone repair significantly influences the spatial distribution and temporal cascade of gene expression, and subsequent cell and tissue differentiation during regeneration. Despite these presumed mechano-biologic relationships and substantial experimental observations, the specific cellular and molecular events associated with the reception and response to biophysical forces remains incompletely characterized. The purpose of this research project is to investigate the mechanoresponsive cells that are involved in the fracture repair process and determine the potential regulatory role of physical forces alone or in concert with a variety of biofactors in enhancing bone regeneration. Utilizing rat models and specialized fracture fixation devices, controlled micro displacements will be applied to fractures crated in femoral diaphyseal bone. We will particularly focus on determining the cell populations that are the sensors and responders to physical forces as a function of time. In addition, using an in situ tissue engineering approach to express local biofactors, we will explore the potential synergistic mechanisms of biologic and biomechanical stimuli. The results of this work may provide us with new insights about the regulators of fracture repair. These insights may lead to the development of new strategies for increasing the rate in which fractures heal and increasing the quality of healing. This might significantly improve healthcare delivery for fractures and reduce work time lost.

描述（由申请人提供）：最近的工作表明，传递到骨修复部位的物理力显着影响基因表达的空间分布和时间级联，以及再生过程中随后的细胞和组织分化。尽管有这些假定的机械生物学关系和大量的实验观察，但与生物物理力的接收和反应相关的特定细胞和分子事件仍然不完全表征。该研究项目的目的是研究参与骨折修复过程的机械反应细胞，并确定物理力单独或与各种生物因子协同作用在增强骨再生中的潜在调节作用。利用大鼠模型和专门的骨折固定装置，受控的微位移将应用于股骨干骨中的骨折。我们将特别关注确定作为时间函数的物理力传感器和响应者的细胞群。此外，利用原位组织工程方法表达局部生物因子，我们将探索生物和生物力学刺激的潜在协同机制。这项工作的结果可能为我们提供有关骨折修复调节因子的新见解。这些见解可能会导致开发新策略，以提高骨折愈合速度并提高愈合质量。这可能会显着改善骨折的医疗服务并减少工作时间损失。