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

仅在美国，每年就有多达150万例与年龄相关的骨折发生，由于目前老年人口的空前增长，预计未来几年骨折将会增加。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，在降低人口破裂风险方面，成果停滞不前。需要新的策略来预防与年龄相关的骨脆性。这一领先的美国繁荣、健康和基础设施工程奖(LEAP-HI)支持通过骨水化降低骨折风险方面的变革性变化的基础研究。增强骨水化的概念是一种新的、有前途的降低骨脆性的途径，它寻求通过结合材料工程、物理、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。这一方法为翻译影响的持续跨学科方法奠定了基础，为广泛的学习者提供了教育机会。该小组将在外联活动中与人口中的特定高危年龄组合作。增强骨水化是降低骨脆性的一条很有前途的途径。这种方法利用了与骨量或密度无关的组织特性。然而，要实现这一方法，还有几个科学障碍需要克服。该奖项支持对水合作用改变局部和组织水平的变形和脆性的生物机制的研究。提出了三个关键的研究问题：(1)深入了解骨骼断裂韧性如何指导水化作为提高骨折韧性的治疗方法？(2)在药物调节条件下，水化骨和水化骨的生物力学特性有何不同？(3)在考虑水化条件的情况下，当前的临床骨折分析预测模型如何变得可预测？将对骨组织标本进行研究，这些标本将接受体外药物治疗以调节水合作用。骨的微结构、矿化以及组织水化的程度和类型将被测量，并与骨在控制和调节状态下的变形和断裂行为相关联，体外发现将扩展到整个骨骼和活体条件。该奖项反映了NSF的法定使命，并通过使用基金会的智力优势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.