CAREER: Understanding the Dynamic Mechanical Adaptations of Bone Tissue at Small Length Scales

该学院早期职业发展(Career)奖支持将力学和高分辨率成像相结合的研究，以揭示人类骨骼如何在动态负荷下适应以防止骨折。在运动、损伤和修复过程中，纳米尺度的骨组织暴露在不断变化的载荷下。然而，目前对骨折的理解框架主要是基于对骨骼健康的静态和宏观评估。定量评估和减轻骨折风险并开出治疗处方的能力需要对纳米尺度上骨组织随时间变化的特性有基本的了解。这项研究将致力于实时解决在模拟从行走到创伤的各种生理条件的动态载荷下，人类骨骼的纳米级成分是如何重新排列和变形的。该项目将研究这种适应在健康和骨质疏松的人体组织中的变化，以了解骨折风险增加的根本原因。在未来，人们希望这种方法将有助于加快对组织进化和骨折方面的治疗的评估。这项工作整合了与当地博物馆和高中教育工作者合作的教育活动，以开发互动模块，向历史上服务不足和代表性不足的高中生教授生物系统的力学和成像。这项研究计划将在生理相关的快速时间尺度上研究纳米级矿化胶原纤维在人骨中的适应性。我们将分析骨在纳米尺度上的动态和非仿射变形，从实验上回答：1)在循环载荷作用下，骨的纳米结构是如何变化的；2)什么机制决定了骨中的动态骨折；3)微尺度组织层次的组成如何对健康和骨质疏松骨的损伤耐受性做出贡献。为了回答1)和2)，该计划将在扫描电子显微镜和同步辐射X射线显微镜上以30纳米和20毫秒的时空分辨率对微米尺寸的骨骼样品进行疲劳和动态断裂实验。小型实验长度标尺将独一无二地允许使用小型人骨活检来回答问题3)。在现有的宏观骨力学的背景下，这项研究将提供并开发本构模型，以演变的动态内聚区的形式来描述相对于裂纹速度的强度和韧性。实验数据将被托管在一个开放源码的储存库中，并有助于促进对细胞外基质如何在细胞无法做出反应和重塑的时间尺度上适应的理解，并进行后续研究以了解这如何影响细胞的命运。该方法将建立一个在长度和时间尺度上调查组织骨折的通用框架。这一裁决反映了NSF的法定使命，并通过使用基金会的智力优势和更广泛的影响审查标准进行评估，被认为值得支持。

This Faculty Early Career Development (CAREER) award supports research that will combine mechanics and high-resolution imaging to uncover how human bones adapt under dynamic loads to prevent fracture. During exercise, injury, and repair, bone tissue at nanometer length scales is exposed to constantly changing loads. However, the current framework for understanding fracture is largely based on static and macroscale assessments of bone health. The ability to quantitatively assess and mitigate fracture risk and prescribe treatment requires a fundamental understanding of time-dependent properties of bone tissue at nanometer length scales. This research will work to resolve in real time how the nanoscale constituents of human bones rearrange and deform, when subjected to dynamic loads that mimic physiological conditions ranging from walking to trauma. The project will investigate how this adaptation varies in healthy and osteoporotic human tissue to understand the fundamental causes of increased fracture risk. In the future, it is hoped that this approach will help accelerate assessment of therapies with respect to tissue evolution and fracture. This work integrates educational activities in partnership with local museums and high school educators, to develop interactive modules that teach mechanics and imaging of biological systems to historically underserved and underrepresented high school students. This research program will investigate the adaptation of nanoscale mineralized collagen fibrils in human bone at physiologically relevant, fast time scales. The dynamic and non-affine deformations of bone at the nanoscale will be analyzed to experimentally answer: 1) how the nanostructure of bone changes under cycling loading 2) what mechanisms dictate dynamic fracture in bone and 3) how the components of microscale tissue hierarchy contribute to damage tolerance in healthy and osteoporotic bone. To answer 1) and 2), the program will develop fatigue and dynamic fracture experiments on micron-sized bone samples in scanning electron and synchrotron X-ray microscopes with 30 nm and 20 ms spatio-temporal resolution. The small experimental length scales will uniquely allow the use of small human bone biopsies to answer question 3). In the context of pre-existing macroscale bone mechanics, the research will inform and develop constitutive models to describe strength and toughness with respect to crack velocity in the form of an evolving dynamic cohesive zone. The experimental data will be hosted in an open-source repository and help advance the understanding of how the extracellular matrix adapts at timescales too fast for cells to respond and remodel, with follow-up studies to understand how this impacts cell fate. The approach will establish a generalizable framework for investigating tissue fracture across length and time scales.This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.