Role of Microstructure in Nanomechanical Behavior of Bone Tissue

描述（由申请人提供）：骨组织是一种异质材料，其特性在骨骼内随时间和空间变化。骨质疏松症等疾病不仅影响骨量，而且影响组织质量。因此，在母基金（R 01-AR 053571）中检查了组织成分对骨机械性能的贡献，重点是了解疾病的影响和确定有效的治疗方法。长骨的发育和纵向生长通过生长板软骨的骨化发生。与骨骼和其他骨骼组织相比，人们对生长板的力学行为知之甚少。对于这次修订，我们建议将我们的组织表征范式扩展到骨生长板的软骨，这是一种具有独特的带状结构的组织，与其生理功能密切相关。特别是，我们将使用一种称为共焦应变映射的技术来可视化生长板在负载下的变形，以了解这种带状组织结构对机械行为的贡献。此外，我们还将利用傅里叶变换红外光谱（FTIR）技术来量化生长板的主要结构成分，胶原蛋白，蛋白多糖和矿物质的带状分布，共聚焦应变映射和FTIR光谱将使我们能够表征生长板中局部结构和性质之间的关系。为了完成这项具有挑战性的任务，我们组建了一支由工程师、物理科学家和生物学家组成的跨学科团队，他们在成像和图像分析、硬组织和软组织表征、生长板生物学、材料测试和儿科骨科方面拥有集体专业知识。在生长板的结构-性能关系的表征将在两个特定的目标进行调查。目标1将使用共聚焦应变映射和FTIR光谱来表征正常生长大鼠生长板的力学行为和结构，而目标2将使用这些相同的技术来研究膳食维生素D缺乏对生长板局部力学行为和结构的影响。已知维生素D缺乏对生长板结构、骨矿化以及如通过母基金所示的骨结构和组织机械特性具有深远影响。因此，本修订版中提出的工作将对生长板功能和骨骼异常之间的联系提供独特的见解，并为理解生长板的生理学以及遗传和环境因素对该组织机械性能的影响提供新的框架。

DESCRIPTION (provided by applicant): Bone tissue is a heterogeneous material with properties that vary spatially and temporally within the skeleton. Diseases such as osteoporosis affect not only bone quantity but also tissue quality. Therefore, the contribution of tissue composition to bone mechanical properties is being examined in the parent grant (R01-AR053571), with an emphasis on understanding the impact of disease and determining effective treatments. The development and longitudinal growth of long bones occurs through ossification of the cartilage of the growth plate. In contrast to bone and other skeletal tissues, relatively little is known about the mechanical behavior of the growth plate. For this revision we propose to extend our tissue characterization paradigm for bone to the cartilage of the growth plate, a tissue with a unique zonal structure that is strongly linked to its physiologic function. In particular, we will use a technique known as confocal strain mapping to visualize the deformation of the growth plate under load to understand the contribution of this zonal tissue structure to mechanical behavior. In addition, we will use established Fourier Transform Infrared (FTIR) spectroscopy techniques to quantify the zonal distribution of the main structural components of the growth plate, collagen, proteoglycans, and mineral. Together, confocal strain mapping and FTIR spectroscopy will enable us to characterize the relationship between local structure and properties in the growth plate. To accomplish this challenging task, we have assembled an interdisciplinary team of engineers, physical scientists, and biologists with collective expertise in imaging and image analysis, hard and soft tissue characterization, growth plate biology, materials testing and pediatric orthopaedics. The characterization of structure-property relationships in the growth plate will be investigated in two specific aims. Aim 1 will use confocal strain mapping and FTIR spectroscopy to characterize the mechanical behavior and structure of the growth plate of normal growing rats, while Aim 2 will use these same techniques to investigate the effect of dietary vitamin D deficiency on the local mechanical behavior and structure of the growth plate. Vitamin D deficiency is known to have profound affects on growth plate structure, bone mineralization, and, as shown through the parent grant, bone structure and tissue mechanical properties. As such, the work proposed in this revision will give unique insight into the connection between growth plate function and skeletal abnormalities as well as providing a new framework for understanding the physiology of the growth plate and the influence of genetic and environmental factors on this tissue's mechanical performance.