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

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导致微损伤累积，这降低了骨的整体质量，并导致刚度降低和机械应变随持续负荷的增加而增加。如果没有足够的骨修复，微损伤的积累最终可能导致疲劳骨折。疲劳性骨折在人类中有很好的记录，但了解甚少。有些人假设，骨重建，响应于微损伤，可能会产生局部孔隙和机械应变升高，导致骨修复和微损伤之间的正反馈回路，最终导致疲劳骨折。本申请的目的是申请资金，用于制造定制的机械测试装置，以在体内无创地循环加载动物后肢。该装置将提供独特的和新颖的见解的作用，细胞重塑活动在疲劳损伤和失败的过程中发挥的骨。该设备将是完全移动的，允许在多个设施中进行实验，包括卡尔加里大学的人类性能实验室和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，可以进行高分辨率的骨纵向测量。所请求的设备将支持卡尔加里大学舒利克工程学院和卡明医学院运动机能学系的爱德华兹博士，以及人类表现实验室和麦凯格研究所的其他主要用户。骨和关节健康，拥有自然科学和工程研究项目。沿着。Edwards博士的研究计划在全骨和骨组织的断裂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作为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生物学的潜在重要方面。这项研究不一定是针对骨的，可能与其他具有层次组织的生物纤维基复合材料有关。所要求的基础设施将立即促进爱德华兹博士的研究计划，并显着增加他的学员的工作范围和影响。如果拟议中的技术基础设施得不到，他的实验室就有可能将这个令人兴奋的机会拱手让给相互竞争的国际研究团体。总而言之，拟议的设备将有助于确保人类绩效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，并为学员提供竞争优势，为学术界，工业界和其他领域的未来职业生涯。

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.