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

仅在美国，每年就有多达150万例与年龄有关的骨折发生，由于目前老年人口的空前增长，预计未来几年骨折病例还会增加。因此，美国正在进入一场迫在眉睫的医疗和经济危机，有可能削弱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，结果在降低人群骨折风险方面停滞不前。有必要采取新的策略来防止与年龄有关的骨骼脆弱。美国繁荣、健康和基础设施领先工程（LEAP-HI）奖支持通过骨水合作用降低骨折风险的变革性变化的基础研究。增强骨水化的概念是一种新颖而有前途的途径，旨在通过结合材料工程、物理学、力学、生物学和生物医学科学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方法，为广泛的学习者提供教育机会。该小组将在外联活动中与人口中特定的高危年龄组合作。增强骨水合作用是降低骨脆弱性的一个有希望的途径。这种方法利用了与骨量或骨密度无关的组织特性。然而，要实现这种方法，还有几个科学障碍需要克服。该奖项支持通过水合作用改变局部和组织水平变形和脆弱性的生物机制研究。本文解决了三个关键的研究问题：(1)如何深入了解骨折韧性，引导水合作用作为一种增加骨折恢复力的治疗方法的部署？(2)在药物调节条件下，水合骨与水合骨的生物力学特性有何不同？(3)目前的骨折分析临床预测模型如何在考虑水化条件的情况下变得具有预测性？研究将在骨组织标本上进行，这些骨组织标本将接受离体药物治疗来调节水化。骨微结构、矿化和组织水化程度和类型将被测量，并与控制和调节状态下骨的变形和骨折行为相关联，离体研究将扩展到整个骨和体内条件。该奖项反映了美国国家科学基金会的法定使命，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。

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.