Multi-scale Characteristics of Bone Toughness

骨韧性的多尺度特征

• 批准号: 1436436
• 负责人: Sandra Shefelbine
• 金额: $ 38.36万
• 依托单位: Northeastern University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2014
• 资助国家: 美国
• 起止时间: 2014-09-01 至 2018-08-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1436436&HistoricalAwards=false
• 关键词: Multi; scale; Characteristics; Bone; Toughness

Bone is both strong and tough because of its unique composition and structure. Bone is composed of two main building blocks: a hard mineral and a soft protein. These building blocks are organized in distinct ways from the molecular level up to the whole bone level, forming a hierarchical composite. Alterations of the composition or organization of the building blocks results in bones that are weak or brittle, but the specific way this happens is not known. The objective of our research is to understand how alterations across levels of hierarchy affect the strength and toughness of bone. The insights gained will help define the critical characteristics of bone toughness, from which we can determine why bone fails in aging and disease. In the scope of this project we will bring the excitement of bones and materials research to the public through 1) adult community education outreach seminars, 2) involving high school summer students in the research, and 3) developing an elementary school science module on "why things break." The objective of this research is to determine the structural, compositional, and mechanical properties of bones at the whole bone (mm), tissue (micron), fibril (nm), and molecular (Angstrom) length scales. We will examine various mouse strains that have altered proteins (transgenic, genetic mutations, and knock-out models) compared to wild type mice. The altered proteins may be the building blocks themselves (such as collagen defects in brittle bone disease) or proteins that are essential to organization and mineralization processes (such as crosslinking proteins) that affect strength and toughness of the bone. At the whole bone level we will determine resistance curves, which characterize both initiation and propagation toughness, from notched 3-point bending. At the tissue level we will examine mineral density with quantitative backscatter scanning electron microscopy and map the elastic modulus to define heterogeneity of material properties. At the fibril level we will examine the mechanics of unmineralized collagen (from tail tendon of the same mice) with dynamic mechanical analysis and mineralized collagen fibrils with small angle x-ray scattering. At the molecular level we will measure crosslinking and non-collagenous proteins. This multi-scale analysis of mechanical, structural, and compositional properties will identify the factors contributing to bone strength and toughness.

骨骼由于其独特的组成和结构而既坚固又坚韧。 骨骼由两种主要的组成部分组成：硬矿物质和软蛋白质。 这些构建模块以不同的方式从分子水平到整个骨骼水平进行组织，形成分层复合材料。结构单元的组成或组织的改变导致骨骼脆弱或易碎，但这种情况发生的具体方式尚不清楚。 我们研究的目的是了解不同层次的改变如何影响骨骼的强度和韧性。 所获得的见解将有助于定义骨骼韧性的关键特征，从中我们可以确定骨骼在衰老和疾病中失败的原因。 在这个项目的范围内，我们将通过1）成人社区教育外展研讨会，2）让高中暑期学生参与研究，以及3）开发一个关于“为什么事情会破裂”的小学科学模块，为公众带来骨骼和材料研究的兴奋。“这项研究的目的是确定骨骼在整个骨骼（mm），组织（微米），原纤维（nm）和分子（埃）长度尺度上的结构，成分和机械特性。 我们将研究与野生型小鼠相比具有改变的蛋白质（转基因、基因突变和敲除模型）的各种小鼠品系。改变的蛋白质可能是构建模块本身（如脆骨病中的胶原蛋白缺陷）或对影响骨强度和韧性的组织和矿化过程至关重要的蛋白质（如交联蛋白）。 在整个骨水平，我们将确定阻力曲线，其表征起始和扩展韧性，从缺口三点弯曲。 在组织水平上，我们将用定量背散射扫描电子显微镜检查矿物质密度，并绘制弹性模量图，以确定材料特性的异质性。 在原纤维水平上，我们将用动态力学分析来检查未矿化胶原蛋白（来自同一小鼠的尾腱）的力学，并用小角度X射线散射来检查矿化胶原蛋白原纤维。 在分子水平上，我们将测量交联和非胶原蛋白。 这种对机械、结构和成分特性的多尺度分析将确定影响骨强度和韧性的因素。