Characterization of the Mechanical Environment of Bone Marrow During Skeletal Loading

这个奖项的目的是了解如何在髋关节骨小梁或松质骨的压力和运动的骨髓是受步行过程中的力量。髋关节中的骨髓是成人中发现造血（血液形成）和间充质（骨骼组织形成）干细胞的主要场所之一，尽管它们的数量随着年龄的增长而下降。研究表明，间充质干细胞虽然数量很少，但对机械刺激高度敏感，但它们在体内经历的刺激的类型和幅度在很大程度上是未知的。将进行一项实验研究，以测量在模拟行走过程中髋关节内不同位置的压力。来自实验的数据将被纳入计算模型，以估计整个骨骼的压力。第二组模型将采用这些计算出的压力来确定微观尺度下骨髓的运动，以及骨髓中机械刺激的分布。如果成功的话，这些研究将提供深入了解骨髓的机械环境和每天给予成体干细胞的压力范围。这些结果将通过提供基线刺激水平来改善细胞培养实验和组织工程构建体的解释和设计。它们还可以提供对骨髓变化的洞察，例如间充质干细胞群体随年龄的下降。最后，计算模型可用于预测响应于异常载荷或疾病条件的行为。为了将该项目的影响扩大到更广泛的社区，一名高中教师将参与研究，项目小组将帮助他们将方法和研究结果纳入课程和项目。

The objective of this award is to understand how the pressure and motion of bone marrow within the trabecular - or spongy - bone in the hip are affected by forces during walking. The bone marrow in the hip is one of the main sites where hematopoietic (blood forming) and mesenchymal (skeletal tissue forming) stem cells are found in adults, although their numbers decline with age. Studies have demonstrated that mesenchymal stem cells, while few in number, are highly sensitive to mechanical stimulation, but the types and magnitudes of stimuli they experience in the body are largely unknown. An experimental study will be conducted to measure the pressure at different locations within the hip during simulated walking. Data from the experiments will be incorporated into computational models to estimate the pressure throughout the bone. A second set of models will employ these calculated pressures to determine the motion of the marrow at the microscopic scale, and the distribution of mechanical stimuli in the marrow. If successful, these studies will provide insight into the mechanical environment of bone marrow and the range of stresses that are imparted to adult stem cells on a daily basis. These results will improve interpretation and design of cell culture experiments and tissue engineering constructs by providing baseline stimulus levels. They may also provide insight into changes in the bone marrow, such as the decline in the mesenchymal stem cell population with age. Finally, the computational models can be used to predict the behavior in response to abnormal loading or disease conditions. To extend the impact of this project to the wider community, a high-school teacher will participate in the research, and the project team will help them incorporate the methods and findings into courses and projects.