LEAP-HI: Engineering New Solutions to Reduce the Burden of Skeletal Fracture

LEAP-HI：设计新的解决方案以减轻骨骼骨折的负担

• 批准号: 1952993
• 负责人: Thomas Siegmund
• 金额: $ 199.7万
• 依托单位: Purdue University
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-06-01 至 2025-05-31
• 项目状态: 未结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1952993&HistoricalAwards=false
• 关键词: LEAP; HI; Engineering; New; Solutions

Each year in the USA alone up to 1.5 million age-related bone fractures occur and bone fractures are expected to increase in the coming years due to the current unprecedented growth in the elderly population. Thus, the nation is entering a looming medical and economic crisis threatening to weaken America’s quality of life and prosperity. Medical treatments have focused on reducing fracture risk by maximizing bone quantity. Yet, outcomes have stalled at a modest level of impact on reducing population fracture risk. There is a need for new strategies to prevent age-related bone fragility. This Leading Engineering for America's Prosperity, Health, and Infrastructure (LEAP-HI) award supports fundamental research on transformational changes in reducing fracture risk through bone hydration. The concept of enhanced bone hydration is a novel and promising pathway to reduce bone fragility that seeks to improve the quality of bone tissue by combining expertise in materials engineering, physics, mechanics, biology, and biomedical sciences. This approach underpins a sustained interdisciplinary approach for translational impact that provides educational opportunities for a broad range of learners. The team will work with the specific at-risk age group of the population in outreach engagements. Enhanced bone hydration is a promising pathway to reduce bone fragility. This approach leverages tissue properties that are independent of bone mass or density. Yet, there are several scientific barriers to overcome to realize this approach. This award supports research on the biomechanisms through which hydration alters local and tissue-level deformation and fragility. Three key research questions are addressed: (1) How can in-depth understanding of bone fracture toughness guide deployment of hydration as a therapeutic approach to increase bone fracture resilience? (2) What are the differences in biomechanical properties of water-hydrated bone vs bone hydrated under pharmacologically modulated conditions? (3) How can current clinical prediction models for bone fracture analysis become predictive under consideration of hydration conditions? Research will be conducted on bone tissue specimens that will be subjected to ex vivo pharmacologically treatment to modulate hydration. Bone microstructure, mineralization and degree and type of tissue hydration will be measured and correlated to the deformation and fracture behavior bone in the control and modulated state and ex vivo finding will be extended to whole bone and in vivo conditions.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.

仅在美国，每年就有多达 150 万起与年龄相关的骨折发生，并且由于目前老年人口空前增长，预计未来几年骨折数量还会增加。因此，国家正在陷入迫在眉睫的医疗和经济危机，威胁到美国的生活质量和繁荣。医学治疗的重点是通过最大限度地增加骨量来降低骨折风险。然而，结果却停滞不前，对降低人群骨折风险的影响有限。需要新的策略来预防与年龄相关的骨脆性。这项美国繁荣、健康和基础设施领先工程 (LEAP-HI) 奖项支持通过骨水合降低骨折风险的变革性基础研究。增强骨水合作用的概念是一种新颖且有前途的降低骨脆性的途径，旨在通过结合材料工程、物理、力学、生物学和生物医学领域的专业知识来提高骨组织的质量。这种方法支持持续的跨学科转化影响方法，为广泛的学习者提供教育机会。该团队将与特定的高危年龄群体合作开展外展活动。增强骨水合作用是降低骨脆性的一种有前景的途径。这种方法利用了与骨量或密度无关的组织特性。然而，要实现这种方法还需要克服一些科学障碍。该奖项支持对水合作用改变局部和组织水平变形和脆性的生物机制的研究。解决了三个关键的研究问题：（1）对骨折韧性的深入了解如何指导将水合作为增加骨折弹性的治疗方法？ (2) 在药理调节条件下，水合骨与水合骨的生物力学特性有何差异？ (3) 当前的骨折分析临床预测模型如何在考虑水合条件的情况下变得具有预测性？研究将对骨组织样本进行研究，这些样本将接受离体药理学处理以调节水合作用。将测量骨的微结构、矿化以及组织水合的程度和类型，并将其与控制和调制状态下骨的变形和断裂行为相关联，离体发现将扩展到整个骨和体内条件。该奖项反映了 NSF 的法定使命，并通过使用基金会的智力价值和更广泛的影响审查标准进行评估，被认为值得支持。

项目成果

Bone hydration: How we can evaluate it, what can it tell us, and is it an effective therapeutic target?

• DOI: 10.1016/j.bonr.2021.101161
• 发表时间: 2022-06
• 期刊: Bone reports
• 影响因子: 2.5
• 作者: Surowiec RK;Allen MR;Wallace JM
• 通讯作者: Wallace JM

A numerical study of dehydration induced fracture toughness degradation in human cortical bone

• DOI: 10.1016/j.jmbbm.2024.106468
• 发表时间: 2024-03-16
• 期刊: JOURNAL OF THE MECHANICAL BEHAVIOR OF BIOMEDICAL MATERIALS
• 影响因子: 3.9
• 作者: Shin，Mihee;Martens，Penny J.;Gludovatz，Bernd
• 通讯作者: Gludovatz，Bernd