Prediction of the Post Yield Behavior of Bone

描述（由申请人提供）：由于骨骼质量的恶化，骨骼骨折倾向的增加是老年人医疗保健中的一个主要问题。由于衰老或疾病导致的骨细胞和/或分子变化最有可能反映在骨成分的超微结构和材料特性（即矿物质和胶原相）上，这些变化最终会影响屈服后的行为（微损伤形成）和组织质量。作为衡量骨质量的主要指标，骨的韧性主要取决于组织屈服后的行为。已有研究表明，骨的屈服后变形很可能是通过两种微损伤的形成来实现的：微裂纹和弥漫性损伤。因此，阐明这些微损伤的产生机制及其与骨成分的关系将大大促进对年龄和疾病相关骨折的理解。尽管骨成分的超微结构和材料特性很可能与骨微损伤的形成有关，但其潜在机制尚不清楚。为了解决这一问题，本研究提出了一种新的矿物-胶原复合材料的概率损伤模型，该模型可用于研究骨组织的拉伸屈服后行为（即纳米/微损伤形成）的机制，并进一步评估骨成分的超微结构和材料特性对这一过程的贡献。本研究的假设是骨微损伤的形成（微裂或弥漫性损伤）取决于组织中胶原原纤维和矿物基质的超微结构和材料特性。目标1：开发矿物-胶原纤维复合材料的概率失效模型，以预测骨骼损伤形成机制（即微裂纹或弥漫性损伤），作为矿物和胶原成分的超微结构和材料特性的函数；为此，将微观力学与概率损伤力学方法相结合，建立矿物-胶原纤维复合材料的概率损伤模型。使用这种新颖的模型，微损伤进展模式作为骨成分的超微结构和材料特性的功能将被检查。目的2：利用几种小鼠模型的骨样本验证概率破坏模型：几种具有不同矿物和胶原相特性的小鼠模型（即C57BL/6， C3HE/H和oim小鼠）将被用来测试矿物和胶原相的超微结构和材料特性对骨屈服后行为（即微损伤形成）的影响。这些实验数据将与Aim 1中开发的机制模型的预测结果进行比较。本研究将首次提供一种新的概率损伤力学方法来研究骨成分的超微结构和材料特性对骨屈服后行为的影响。此外，该模型将为年龄和疾病相关骨折的潜在机制提供重要见解。阐明这些基本问题不仅具有重要的科学意义，而且对预测和预防与年龄有关的骨质疏松性骨折的策略的未来发展也具有重要意义。

DESCRIPTION (provided by applicant): The increased skeletal propensity to fracture is a major concern in health care of elderly populations due to the deteriorated bone quality. Cellular and/or molecular changes in bone due to aging or diseases are most likely reflected in the ultrastructure and material properties of bone constituents (i.e., mineral and collagen phases), which would eventually affect the post-yield behavior (microdamage formation) and the quality of the tissue. As a major measure of bone quality, the toughness of bone is mainly determined by the post-yield behavior of the tissue. Previous studies have demonstrated that the post-yield deformation of bone is most likely realized through the formation of two types of microdamages: microcrack and diffuse damage. Thus, elucidating the generating mechanisms of these microdamages and its relationship with bone constituents would significantly facilitate the understanding of age and disease related bone fractures. Although the ultrastructural and material properties of bone constituents is most likely related to the microdamage formation in bone, the underlying mechanism is poorly understood. To address this issue, the present study proposes a novel probabilistic damage model of mineral-collagen composites that can be used to study the mechanism of the tensile post-yield behavior (i.e., nano/microdamage formation) for bone tissues, and further to assess the contribution of ultrastructural and material properties of the bone constituents to the process. The hypothesis of this study is that microdamage formation (microcrack or diffuse damage) in bone is dependent on the ultrastructural and material properties of collagen fibrils and mineral matrix in the tissue. Two specific aims will be addressed as follows: Aim1: To develop a probabilistic failure model of mineral-collagen fibril composite to predict the mechanisms of damage formation in bone (i.e., either microcrack or diffuse damage) as a function of ultrastructural and material properties of mineral and collagen constituents: To do so, micromechanics combined with the probabilistic damage mechanics approaches will be used to develop a probabilistic damage model of mineral-collagen fibril composites. Using this novel model, patterns of microdamage progression as a function of ultrastructural and material properties of bone constituents will be examined. Aim 2: To verify the probabilistic failure model using bone samples from several mice models: Several mice models (i.e., C57BL/6, C3HE/H, and oim mice) with varied properties of the mineral and collagen phases will be utilized to test the effects of ultrastructural and material properties of the mineral and collagen phases on the post-yield behavior of bone (i.e., microdamage formation). These experimental data will be compared with the predictions by the mechanistic model developed in Aim 1. This study will, for the first time, provide a novel probabilistic damage mechanics approach to examine the effect of ultrastructural and material properties of bone constituents on the post-yield behavior of bone. Moreover, this model will provide significant insights into the underlying mechanism of age and disease related bone fractures. Elucidating these fundamental issues is not only scientifically important, but also give rise to the future development of strategies in prediction and prevention of age-related and osteoporotic bone fractures.