Understanding bone strength and fracture by multiscale modeling, testing and imaging: the role of chemical composition and hierarchical structure

我的研究计划是通过多尺度计算建模，力学测试和成像来研究骨强度和骨折。骨折由骨强度和所施加的力决定，而骨强度又由骨的化学组成和结构决定。骨具有复杂的化学成分和层次化的纳微结构。现有的理论和模型是从以前的研究中建立的，这些研究大多是在宏观尺度上使用整个骨骼或骨骼标本进行的，我们仍然不知道宏观尺度上的骨骼强度如何定量地受到化学成分和纳米-微米结构的影响，以及冲击力如何导致骨骼特定部位的骨折。为了更好地了解骨强度和骨折，人们必须了解这种迷人材料在分子，细胞，组织，器官和全身水平上的层次结构，并了解身体周围的机械环境。生物力学和生物医学研究人员还有很长的路要走。多尺度建模是理解骨力学行为的一种很有前途的方法，但仍处于发展阶段。我的研究计划的长期目标是为骨强度和骨折的多尺度理论和模型的建立做出贡献。在我上一个发现基金（DG）的任期内，我开发了一个宏观层次的三级生物力学模型，以了解跌倒引起的髋部骨折的生物力学。我的下一个DG任期的短期目标是研究更小长度尺度的骨强度和骨折，即了解骨化学成分（矿物质，有机物和水）和纳米微结构（孔隙和晶体尺寸）如何影响骨强度和骨折。该研究将有助于：（1）建立不同尺度下骨刚度/强度与化学成分/结构之间的关系;（2）建立骨强度和骨折的多尺度生物力学模型。 拟议的研究将对生物力学/生物医学工程和材料工程的社区产生重大影响。例如，骨强度和骨折的多尺度模型将有助于生物力学工程师提高载人飞行器保护装置的有效性。骨刚度/强度与化学成分/结构之间的关系将有助于生物医学工程师改善骨折风险的评估和3D打印骨工艺品的设计;它还将激励材料工程师设计新型高效的复合材料。在拟议的研究中训练有素的高素质人员将配备材料多尺度建模的尖端知识和技术，这对于生物力学/生物医学和材料工程的创新是必要的。

My research program is to study bone strength and fracture by multiscale computational modeling, mechanical testing and imaging. Bone fracture is determined by bone strength and the applied force, and bone strength is in turn determined by bone chemical composition and architecture. Bone has complicated chemical compositions and hierarchical nano-micro-structures. With the existing theories and models established from previous studies that were mostly conducted at macroscale using whole bones or bone specimens, we still do not know how bone strength at macroscale are quantitatively affected by chemical compositions and nano-micro-structures, and how an impact force causes a fracture at a specific site of a bone. To better understand bone strength and fracture, one has to understand the hierarchical architecture of this fascinating material at the molecular, cellular, tissue, organ, and whole body levels, in conjunction with an understanding of the mechanical environment surrounding the body. It is still a long way for biomechanical and biomedical researchers to go. Multiscale modeling is a promising method to understand bone mechanical behavior, but it is still under development. The long-term objective of my research program is to contribute to the establishment of multiscale theories and models for bone strength and fracture. In my previous Discovery Grant (DG) term, I developed a hierarchy of three-level biomechanical models at macroscale to understand the biomechanics involved in fall-induced hip fracture. The short-term objective of my next DG term is to study bone strength and fracture at smaller length scales, i.e. to understand how bone chemical composition (mineral, organic matter and water) and nano-micro-structure (pores and crystal sizes) affect bone strength and fracture. The proposed research will contribute to: (1) the establishment of relationships between bone stiffness/strength and chemical compositions/structures across different scales; (2) the development of multiscale biomechanical models of bone strength and fracture. The proposed research would have a major impact on the communities of Biomechanical/Biomedical Engineering and Materials Engineering. For example, the multiscale models of bone strength and fracture would help biomechanical engineers improve the effectiveness of protective devices in manned vehicles. The relationships between bone stiffness/strength and chemical compositions/structures would help biomedical engineers improve evaluation of fracture risk and advance design of 3D printed bone crafts; it would also inspire material engineers to design novel and efficient composite materials. Highly qualified personnel trained in the proposed research would be equipped with cutting-edge knowledge and techniques of material multiscale modeling, which will be necessary for innovations in both Biomechanical/Biomedical and Materials Engineering.