Collaborative Research: Aging and Disease Effects on Viscous Energy Dissipation of Bone as Characterized by Nanoindentation

该奖项的研究目标是将一种新兴的动态纳米压痕方法应用于骨骼，以便能够在微米尺度上量化组织粘弹性行为与年龄和疾病相关的变化，以便与其断裂行为相关联。骨的主要成分的组织具有内在的层次性，因此，每个层次都有助于骨骼抵抗骨折的能力。动态纳米压痕和R曲线测试将在板层水平和骨性结构水平上进行，使用来自年轻和老年人类捐赠者的皮质骨、啮齿动物疾病模型和体外改变属性的骨。此外，还将测量骨骼的成分特征，以评估它们对粘弹性和骨折韧性的相对贡献。这项工作有可能证明，衰老和某些疾病(如糖尿病)通过在组织水平上抑制粘性机制导致骨骼消耗较少的能量，从而导致骨骼的整体抗折性降低。此外，这项研究还将推出一套新的工具，用于研究生物组织的小范围变形行为。该计划产生的科学知识将加强该领域的努力，以开发骨质量的分级模型，并确定预防骨折的新治疗目标。该项目汇集了工程学和医学院的多学科团队，为材料科学和生物医学工程领域的研究人员提供了相互交流专业知识的机会。该教育计划的重点是为工程师开辟道路，让他们对医学研究产生影响，并让生物医学研究人员受益于在物理科学中开发的实验方法。

The research objective of this award is to apply an emerging dynamic nanoindentation method to bone so that age- and disease-related changes in the viscoelastic behavior of the tissue can be quantified at the micron length scale for correlation with its fracture behavior. The organization of the primary constituents of bone is inherently hierarchical, and as such, each level contributes to the ability of bone to resist fracture. Dynamic nanoindentation and R-curve testing will be conducted at the level of the lamellae and at the level of the osteonal structure using cortical bone from young and old human donors, rodent models of disease, and bone whose properties have been altered ex vivo. In addition, the compositional characteristics of the bone will be measured to assess their relative contribution to the viscoelastic properties and fracture toughness.This work has the potential to demonstrate that aging and certain diseases such as diabetes cause bone to dissipate less energy by suppression of viscous mechanisms at the tissue-level, thereby contributing to an overall reduction in the fracture resistance of bone. Moreover, the research will introduce a new set of tools for investigating the small-scale deformation behavior of biological tissues. The scientific knowledge generated from this program will enhance efforts in the field to develop hierarchical models of bone quality and to identify new therapeutic targets for fracture prevention. The project brings together an engineering and medical school multidisciplinary team, providing the opportunity for cross-fertilization of expertise from researchers in materials science and biomedical engineering. The educational plan focuses on opening pathways for engineers to make an impact on medical research and biomedical researchers to benefit from experimental approaches developed in the physical sciences.