Multiscale modeling of fatigue-life variation in bone

机械疲劳的定义是材料在循环载荷下的逐渐弱化。这种现象发生在工程和生物材料中，并可能导致结构在加载量级远低于最大破坏载荷时发生破坏。我的研究计划的长期目标是了解并最终预测骨的机械疲劳行为。在上一个资助周期中，我的NSERC DG研究项目取得了重大发现，促进了我们对机械疲劳过程的机理理解。这些发现为我的研究计划的短期目标提供了实践和理论基础，即识别和模拟决定骨骼疲劳强度的结构和微建筑特征。我们的科学方法将在生物力学工程、计算建模、先进成像和材料科学领域采用和推进当前最先进的技术。我的研究项目的独特之处在于，它结合了数值与实验的方法，跨越了从全身到细胞水平的多维尺度。在全身/器官水平上，我们将描述全骨形态和密度的种群差异，最终目标是量化骨应变升高的结构决定因素。在器官/组织水平上，我们将验证全骨疲劳破坏中的应力体积现象，即在给定的应力水平下，较大的骨样本更有可能失败。在组织/细胞水平上，我们将研究临界距离理论，即应力集中只会在应力场超过相关失效过程发生的临界尺寸时导致失效的原理。本提案中概述的目标将提供对骨骼机械疲劳现象的机械理解，这样我们就可以在最复杂的尺度上预测疲劳断裂，即结构水平。所提出的方案是新颖的，因为它远离了传统的骨力学还原论观点，即研究工作集中在骨骼系统的单个维度尺度上的现象。重要的是，该研究项目的发现不仅适用于骨，还适用于其他具有分层组织和复杂结构几何形状的纤维基复合材料，从而降低安全系数或提高设计效率。该计划和环境将为学生提供生物力学和生物医学工程中各种实验，分析和计算方法的专业知识。这将包括机械测试、有限元建模、高级成像分析和计算机编程方面的培训和经验，这些都是非常受欢迎的核心技能，将为未来在学术界、工业界和其他领域的职业生涯提供竞争优势。

Mechanical fatigue is defined as the progressive weakening of a material exposed to cyclic loading. This phenomenon occurs in both engineering and biological materials and may lead to structural failure at loading magnitudes well below maximum failure load. The long-term objective of my research program is to understand and ultimately predict the mechanical fatigue behavior of bone. During the previous funding cycle, my NSERC DG research program made significant discoveries that have advanced our mechanistic understanding of the mechanical fatigue process. These findings have provided both a practical and theoretical foundation for the short-term objectives of my research program, which are to identify and model the structural and microarchitectural features that determine the fatigue strength of bone. Our scientific approach will employ and advance current state-of-the-art technologies in the fields of biomechanical engineering, computational modeling, advanced imaging, and materials science. Unique to my research program is a combined numerical-experimental approach that spans multiple dimensional scales, from the whole-body to the cellular level. At the whole-body/organ level, we will characterize population variance in whole-bone morphology and density, with an end goal to quantify structural determinants of elevated bone strain. At the organ/tissue level, we will verify the phenomenon of stressed volume in the fatigue failure of whole-bone, whereby larger bone samples are more likely to fail at a given stress level. At the tissue/cellular level, we will examine the Critical Distance Theory, i.e., the principal that a stress concentration will only lead to failure when the stress field exceeds a critical size over which relevant failure processes occur. The objectives outlined in this proposal will provide a mechanistic understanding of the mechanical fatigue phenomenon in bone such that we can predict fatigue fracture at its most complex scale, i.e., the structural level. The proposed program is novel in that it moves away from the traditional reductionist view of bone mechanics, whereby investigative efforts focus on phenomena at individual dimensional scales of the skeletal system. Importantly, the findings from this research program are not only specific to bone, but translate to other fibre-based composite materials with hierarchical organization and complex structural geometries allowing for lower safety factors or more efficient design. The proposed program and environment will provide students with expertise in a variety of experimental, analytical, and computational approaches in biomechanics and biomedical engineering. This will include training and experience with mechanical testing, finite element modeling, advanced imaging analysis, and computer programming - highly sought-after core skills that will provide a competitive advantage for future careers in academia, industry and beyond.