CAREER: Multiscale Mechanical Characterization of Bone Fracture Healing

这笔学院早期职业发展(Career)补助金将解决一个重要的尚未解决的生物力学问题：没有一种非侵入性技术来测量活体动物和人类的骨折愈合。这项研究计划将使用计算机断层扫描(CT)来创建解剖上准确的愈合骨骼的3D模型。这些模型将被用来衡量治愈的程度。这些模型还可以检测修复是否失败。这种方法使用工程模拟工具进行虚拟机械测试，将测量愈合骨的机械强度。这将评估愈合情况，而不需要与动物或人类患者进行直接的身体互动。骨骼模型将适应承重，就像骨骼在人体内的行为一样--这是这项工作的一个新特点。这些结果将推动一种新的非侵入性生物力学驱动的方法来测量骨折愈合，并对科学和社会产生影响。对社会的长期好处将是开发类似的工具，比目前可能的更早地发现骨愈合问题，最终可能会以更低的成本获得更好的护理。这项研究与教育推广计划紧密结合在一起。外联活动的目的是在地方和全国范围内改善妇女在机械工程领域的留住情况。研究和教育计划的结合成果将支持研究人员在骨的非侵入性力学特性测量方面的职业生涯。本研究的总体目标是描述骨折痂的结构力学特征，骨痂是一种重要的但研究不足的肌肉骨骼组织。具体的技术目标是：(1)定义和验证用于模拟骨折骨痂的密度依赖的力学特性的比例定律；(2)基于器官级别的刚性和组织级别的应力集中，开发用于检测失败的骨愈合(骨不连)的多轴虚拟力学测试集合；以及(3)表征骨折骨痂的结构组织，并测量骨-骨痂边界的重塑作为愈合速度的定量指标。这项工作将使用新的图像分析算法、结构有限元建模和高性能计算(HPC)支持的优化方法来完成。在这个项目中，我们将展示如何使用常规的临床成像来量化愈合骨折的力学、组织和重塑阶段。通过该计划开发的方法将对研究骨愈合的跨学科研究人员社区产生革命性影响，使其能够对结构愈合进行体内定量评估，并在发生愈合失败时对其进行明确诊断。通过相关的外展活动，该奖项还将在PI的机构内和与Perry倡议的合作伙伴关系中，解决机械工程领域女性代表性不足的循证驱动因素。该奖项反映了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) grant will address an important unsolved biomechanical problem: there is no non-invasive technique to measure bone fracture healing in living animals and humans. This research program will use computed tomography (CT) scans to create anatomically accurate 3D models of healing bones. These models will be used to measure how much healing has occurred. The models can also detect if healing has failed. This approach uses engineering simulation tools to carry out virtual mechanical tests, which will measure the mechanical strength of the healing bone. This will assess healing without the need for direct physical interaction with an animal or human patient. The bone models will adapt to load-bearing just like bones behave in the body - a novel feature of this work. These results will advance a new paradigm of non-invasive biomechanics-driven methods for measuring bone fracture healing and have impact on both science and society. The long-term benefit to society will be to develop similar tools to detect problems with bone healing much earlier than is currently possible, which may ultimately lead to better care at lower cost. The research is closely integrated with an educational outreach plan. Outreach activities are aimed at improving the retention of women in mechanical engineering, both locally and nationally. The combined outcomes of the research and education plans will support the investigator's career in non-invasive mechanical properties measurement of bone.The overall objective of this research is to characterize the structural mechanics of bone fracture callus, an important but under-studied musculoskeletal tissue. The specific technical objectives are: (1) define and validate a scaling law for modeling the density-dependent mechanical properties of fracture callus, (2) develop a collection of multiaxial virtual mechanical tests for detecting failed bone healing (nonunion) based on organ-level rigidity and tissue-level stress concentrations, and (3) characterize the structural organization of fracture callus and measure remodeling at the bone-callus boundary as quantitative indicators of healing speed. This work will be accomplished using new image analysis algorithms, structural finite-element modeling, and high-performance computing (HPC) enabled optimization methods. In this project, we will show how routine clinical imaging can be used to quantify the mechanics, organization, and remodeling stage of a healing fracture. The methods developed through this program will have a transformative impact on the interdisciplinary community of researchers studying bone healing by enabling quantitative in vivo assessment of structural healing and definitive diagnosis of failed healing when it occurs. Through associated outreach activities, this award will also address evidence-based drivers of female under-representation in mechanical engineering, both within the PI’s institution and nationally in partnership with the Perry Initiative.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.