A New Self-healing Mechanism and its Impact on Multiscale Biomechanics of Bone

该奖项的研究目的是探索骨中纳米级自我修复的机制基础，并评估其对骨折的影响。这些研究将大大增加对复杂的生物物理自我修复机制的理解，这些机制正越来越多地被应用于开发先进材料。通过阐明骨质疏松症对骨修复的影响，了解自我修复也将对人类健康产生重大影响，并可能导致对骨质疏松症患者的强化治疗。对物种间和物种内基质蛋白含量的了解将为物种之间的生物力学和矿物质差异提供直接证据，并提供与以前探索不足的规模的骨骼进化有关的推断。该奖项支持的教育计划侧重于开发机械生物学和连续介质力学的新的互动课程内容，这两门课程由PIS在本科生和研究生水平教授。这项研究的结果将直接将跨学科材料引入上述课程。该奖项下进行的研究将使用生化分析和X射线技术来研究非胶原骨蛋白、骨钙素和骨桥蛋白与人类体内和选定动物物种的骨矿相之间的联系。纳米力学测试和原子力显微镜将在体外生理条件下评估和监测骨钙素和骨桥蛋白以及矿物质在修复纳米级损伤中的作用。最后，将使用多尺度建模方法，结合宏观断裂韧性和从多个动物骨骼获得的骨矿数据，全面了解纳米级骨基质自我修复如何影响不同物种的整体骨断裂抗力。

The research objective of this award is to investigate the mechanistic basis of the nanoscale self-repair in bone and evaluate how it impacts the fracture of bone. These studies will add significantly to the understanding of complex biophysical self-healing mechanisms that are increasingly being applied to develop advanced materials. Understanding self-healing will also have a major impact on human health, by elucidating the impact osteoporosis has on bone repair, and may lead to enhanced therapeutic treatments for osteoporotic patients. An understanding of the inter- and intra-species matrix protein content will provide direct evidence of biomechanical and mineral variation between species, providing inferences related to bone evolution on a scale that has previously been under explored. The educational plan supported by this award focuses on developing new and interactive course content in Mechanobiology and Continuum Mechanics, two courses taught by the PIs at the undergraduate and graduate levels. The findings of this study will directly introduce interdisciplinary material to the courses mentioned above.Studies conducted under this award will employ biochemical analyses and x-ray techniques to examine the association between non-collagenous bone proteins, osteocalcin and osteopontin, and the bone mineral phase within humans and across selected animal species. Nanomechanical testing and atomic force microscopy will be used to evaluate and monitor the roles of osteocalcin and osteopontin, and mineral in repairing nanoscale damage, under physiological conditions in vitro. Finally, multi-scale modeling approaches, incorporating macroscale fracture toughness and bone mineral data obtained from bones of multiple animals, will be used to develop a comprehensive understanding of how bone matrix self-healing at the nanoscale, impacts whole bone fracture resistance across various species.