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

职业：了解小长度尺度下骨组织的动态机械适应

• 批准号: 2339836
• 负责人: Ottman Tertuliano
• 金额: $ 71.95万
• 依托单位: University of Pennsylvania
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2024
• 资助国家: 美国
• 起止时间: 2024-05-01 至 2029-04-30
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=2339836&HistoricalAwards=false
• 关键词: CAREER; Understanding; Dynamic; Mechanical; Adaptations

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.

这项教师早期职业发展（职业）奖支持将结合力学和高分辨率成像的研究，以发现人类骨头如何在动态负载下适应以防止骨折。在运动，受伤和修复过程中，纳米长度尺度下的骨组织暴露于不断变化的负载。但是，当前理解断裂的框架主要基于骨骼健康的静态和宏观评估。定量评估和减轻断裂风险和开处方治疗的能力需要对纳米长度尺度下骨组织的时间依赖性特性有基本的理解。这项研究将实时解决人类骨骼的纳米级成分如何重新排列和变形，并承受模仿生理状况从步行到创伤的动态负荷。该项目将研究这种适应性如何在健康和骨质疏松性人体组织中变化，以了解裂缝风险增加的基本原因。将来，希望这种方法将有助于加速对组织进化和断裂的疗法评估。这项工作与当地博物馆和高中教育者合作整合了教育活动，以开发互动模块，以教授生物系统的力学和成像为历史上服务不足和代表性不足的高中生。该研究计划将研究人骨在生理相关的快速时间尺度上的纳米级矿化胶原原纤维的适应。将分析纳米级骨骼的动态和非伴侣变形，以实验回答：1）在循环加载下骨骼变化的纳米结构如何在循环加载下2）哪些机制决定骨骼中的动态骨折和3）3）微观组织层次的成分如何有助于损害健康和骨质骨骼的损伤。要回答1）和2），该程序将在扫描电子中的微米大小的骨样品上开发疲劳和动态断裂实验，并具有30 nm和20 ms时空分辨率的X射线X射线显微镜。较小的实验长度尺度将唯一允许使用小的人骨活检回答问题3）。在预先存在的宏观骨骼力学的背景下，该研究将为构成模型提供信息，以描述以不断发展的动态凝聚区的形式描述裂纹速度的强度和韧性。实验数据将托管在开源存储库中，并有助于促进对细胞外矩阵在时间尺度如何适应细胞无法响应和重塑的情况，并进行后续研究，以了解这如何影响细胞命运。该方法将建立一个可概括的框架，用于调查跨长度和时间尺度的组织骨折。该奖项反映了NSF的法定任务，并被认为是值得通过基金会的知识分子优点和更广泛的影响审查标准通过评估来支持的。