CAREER: Structures and Properties of Bone at Multiple Length Scales

该奖项全部或部分由2021年美国救援计划法案（公法117-2）资助。非技术性概述：骨是一种典型的矿化生物组织，具有上级力学性能。它坚固，坚韧，但重量轻，这可以归因于其层次结构，即多个长度尺度的结构。然而，在亚微米和纳米尺度上的骨结构仍然没有得到很好的理解。在这个项目中，PI建议研究多个长度尺度，特别是亚微米和纳米尺度的骨结构和性能之间的关系。对骨骼的更深入了解可以为骨折预测提供见解，并使老龄人口和骨骼疾病患者受益。10.2 50岁及以上的美国人有100万人患有骨质疏松症，这可能导致骨折风险增加。有关骨骼的新知识还将为设计更坚固的人造材料提供灵感，促进生物医学材料的发展，扩展到其他天然生物复合材料的研究，并对交通、建筑、国防、生物医学和能源等领域的广泛应用产生重大影响。该项目的教育和推广活动将建立一个管道，将更多来自代表性不足的群体的人，特别是女性，纳入STEM领域。技术总结：对骨骼的基本理解可以揭示开发合成材料的挑战，通过多个长度尺度的机制组合，使其既坚固又坚韧。本提案的研究目标是使用综合实验和模型在多个长度尺度上确定骨中的组成-结构-性质关系。核心假设是骨的整体性质（强度、韧性、适应性）与其微观结构（骨水泥线和亚板层）和纳米级超微结构（矿化胶原纤维（MCF）和纤维外基质（EFM））的组成、结构和性质相关。PI将首先开发相关的显微镜技术，以表征骨的超微结构和显微结构的组成、结构和特性。然后在皮质骨和松质骨中，将分别确定跨多个长度尺度的组成-结构-性质。最后，种植体周围的骨适应将在其外在形态和内在属性方面进行研究。教育和推广目标是通过骨教育和推广活动，扩大代表性不足的群体，特别是女性在STEM中的参与。PI正在与当地的科学博物馆合作，为K-12学生，特别是女孩，提供夏令营和课后项目，以了解骨骼。此外，本科生和研究生将接受跨学科（材料和医学）骨骼研究的教育和培训。PI还将创建更多STEM劳动力中女性的在线视频系列。该奖项反映了NSF的法定使命，并通过使用基金会的知识价值和更广泛的影响审查标准进行评估，被认为值得支持。

This award is funded in whole or in part under the American Rescue Plan Act of 2021 (Public Law 117-2).Non-technical Summary:Bone is a typical mineralized biological tissue that exhibits superior mechanical properties. It is strong, tough, yet lightweight, which can be attributed to its hierarchical structures, i.e. structures at multiple length scales. However, the structures in bone at the sub-micron and nano-scales are still not well understood. In this project, the PI proposes to study the relationship between the structure and property of bone across multiple length scales, particularly in the sub-micron and nano-scales. A deeper understanding of bone can provide insights to fracture prediction and benefit the aging population and people with bone disorders. 10.2 million American people aged 50 and over have osteoporosis, which may lead to an increased risk of fracture. The new knowledge about bone will also provide inspirations for the design of more robust manmade materials, enable the advancement in biomedical materials, be extended to the research of other natural biocomposites, and significantly impact the broad range of applications in transportation, buildings, defense, biomedicine, and energy. The education and outreach activities in this project will build a pipeline to include more people from underrepresented groups, especially females, into STEM fields.Technical Summary:Fundamental understandings of bone can shed light on the challenges of developing synthetic materials that are both strong and tough through a combination of mechanisms across multiple length scales. The research objective of this proposal is to determine the composition-structure-property relationships in bone, at multiple length scales using integrated experiments and models. The central hypothesis is that the bulk properties of bone (strength, toughness, adaptation) are related to the composition, structure, and properties in its microscale structures (cement line and sub-lamellae) and nanoscale ultrastructure (mineralized collagen fibril (MCF) and extrafibrillar matrix (EFM)). The PI will first develop correlative microscopy techniques to characterize composition, structure, and properties for ultrastructure and microstructure of bone. Then in cortical bone and trabecular bone, the composition-structure-property across multiple length scales will be determined, respectively. Finally, the peri-implant bone adaptation will be investigated in terms of its extrinsic morphology and intrinsic properties. The education and outreach objective is to broaden participation from underrepresented groups, especially females, in STEM through education and outreach activities on bone. The PI is partnering with a local science museum in summer camps and after-school programs for K-12 students, especially girls, to learn about bone. Also, undergraduate and graduate students will be educated and trained on interdisciplinary (materials and medicine) bone research. The PI will also create more online video series of females in STEM workforce.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.