A non-invasive loading device to examine the role of mechanobiology in the fatigue failure process of bone

一种非侵入性加载装置，用于检查力学生物学在骨疲劳破坏过程中的作用

• 批准号: RTI-2022-00038
• 负责人: Edwards, William
• 金额: $ 7.44万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Research Tools and Instruments
• 财政年份: 2021
• 资助国家: 加拿大
• 起止时间: 2021-01-01 至 2022-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=741780
• 关键词: non; invasive; loading; device; examine

Mechanical fatigue of load bearing bone is an inevitable consequence of physical activity. Habitual loading of the skeletal system causes microdamage accumulation that reduces the overall quality of bone and leads to a reduction in stiffness and an increase in mechanical strain with continued loading. Without adequate bone repair, the accumulation of microdamage may eventually lead to fatigue fracture. Fatigue fractures in bone are well documented in humans but poorly understood. Some have postulated that bone remodeling, in response to microdamage, may create localized porosity and elevated mechanical strain resulting in a positive feedback loop between bone repair and microdamage, ultimately resulting in fatigue fracture. The objective of this application is to request funds for the fabrication of a custom mechanical testing device to noninvasively, cyclically load animal hindlimbs in vivo. The device will provide unique and novel insight into the role that cellular remodeling activity plays in the fatigue damage and failure process of bone. The device will be completely mobile, allowing for experimentation across multiple facilities including the Human Performance Lab and the Interdisciplinary Science and Innovation Centre building at the University of Calgary, a facility equipped with an in vivo micro-computed tomography scanner allowing for high-resolution, longitudinal measurements of bone. The requested device will support Dr. Edwards within the Faculty of Kinesiology, Schulich School of Engineering, and Cumming School of Medicine at the University of Calgary, along with other major users in the Human Performance Lab and McCaig Institute for Bone and Joint Health that have natural science and engineering research programs. Dr. Edwards' research program has made significant advancements and discoveries related to the fracture and fatigue of whole bone and bone tissue; however, his current ex vivo approach is limited to a basic understanding of bone as an inert material and is thus an unable to account for potentially important aspects of biology in the fatigue damage and failure process. This research is not necessarily specific to bone and may be relevant to other biological fiber-based composite materials with hierarchical organization. The requested infrastructure would immediately catalyze Dr. Edwards' research program and significantly increase the scope and impact of his trainees' work. If the proposed technical infrastructure is not acquired, his lab risks ceding this exciting opportunity to competing international research groups. To summarize, the proposed equipment will help to ensure the continued success and international reputation of the Human Performance Lab, allow the next generation of young scientists a chance to ask new and important questions in an inclusive and diverse environment, and provide trainees a competitive advantage for future careers in academia, industry, and beyond.

承重骨的机械疲劳是体力活动的必然结果。骨骼系统的习惯性负荷会导致微小损伤的积累，从而降低骨骼的整体质量，并导致僵硬的减少和机械应变的增加。如果没有足够的骨修复，微损伤的积累最终可能导致疲劳性骨折。骨骼疲劳骨折在人类中得到了很好的记录，但人们对此了解很少。一些人推测，骨重建对微损伤的反应可能会产生局部孔洞和机械应变增加，导致骨修复和微损伤之间的正反馈循环，最终导致疲劳性骨折。这项申请的目的是申请资金，以制造一种定制的机械测试设备，以非侵入性的、在活体内循环加载动物后肢。该设备将为细胞重塑活动在骨骼疲劳损伤和失效过程中所起的作用提供独特和新颖的见解。该设备将完全移动，允许在多个设施中进行实验，包括人类行为实验室和卡尔加里大学的跨学科科学与创新中心大楼，该设施配备了体内微型计算机断层扫描仪，可以对骨骼进行高分辨率的纵向测量。申请的设备将支持卡尔加里大学运动学学院、舒利赫工程学院和卡明医学院的爱德华兹博士，以及拥有自然科学和工程研究项目的人类性能实验室和麦凯格骨与关节健康研究所的其他主要用户。爱德华兹博士的研究计划在整个骨骼和骨组织的骨折和疲劳方面取得了重大进展和发现；然而，他目前的体外方法仅限于对骨骼作为一种惰性材料的基本理解，因此无法解释疲劳损伤和失效过程中潜在的重要生物学方面。这项研究不一定是针对骨骼的，可能与其他具有层次化组织的生物纤维基复合材料相关。所要求的基础设施将立即促进爱德华兹博士的研究计划，并显著增加他的受训人员工作的范围和影响。如果不能获得拟议的技术基础设施，他的实验室可能会将这一令人兴奋的机会让给相互竞争的国际研究集团。总之，拟议的设备将有助于确保人类性能实验室的持续成功和国际声誉，让下一代年轻科学家有机会在包容和多样化的环境中提出新的重要问题，并为学员在未来的学术界、工业界和其他领域的职业生涯提供竞争优势。