Mechanical Factors and Cellular Responsiveness in Fracture Repair

描述(申请人提供)：最近的研究表明，传递到骨修复部位的物理力显著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-生物关系和大量的实验观察，但与生物物理力的接收和响应相关的特定细胞和分子事件仍然没有完全表征。这项研究的目的是研究参与骨折修复过程的机械反应细胞，并确定物理力量单独或与各种生物因子协同作用在促进骨再生方面的潜在调节作用。利用大鼠模型和专门的骨折固定装置，可控制的微小位移将应用于股骨骨干骨折。我们将特别侧重于确定作为时间函数的物理力的传感器和响应者的细胞数量。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关于骨折修复调节因素的新见解。这些洞察力可能会导致开发新的策略，以提高骨折愈合的速度和质量。这可能会显著改善骨折的医疗保健服务，并减少工作时间损失。

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.