ERI: Reimagining the Use of Animal Models in Musculoskeletal Research

在生物力学研究中，动物对象经常被用作人类的替代品。这通常是由于动物实验对象之间的低可变性、低成本和跨物种的高生物相似性而被证明是合理的。虽然动物组织的生物学，如软骨和韧带，已经得到了广泛的研究，但人们对正常活动中作用于它们的力往往知之甚少。这项研究将利用这样一个事实，即一些动物组织承受的负荷范围比人类要小得多，以得出负荷与组织结构之间的联系。这一工程研究启动(ERI)项目将通过活体动物运动跟踪和计算机建模相结合的方式，全天检查作用于牛尾不同圆盘上的载荷。这项工作将建立动物模型，作为研究力学和生物学之间相互作用的理想系统。这项研究的结果将通过为患者特定的模型做出贡献来减轻下腰痛的社会负担，这将能够确定负荷模式的变化，如职业的变化。这项工作将通过当地社区的科学咖啡馆系列向成年公民科学家展示，并通过一年一度的大学主办的科学和工程博览会向年轻科学家展示。该项目旨在检查牛尾侧椎间盘，以了解组织结构和体内负荷历史之间的关系。体内负荷一直是研究组织对负荷反应的重塑过程的一个关键限制。这项研究将重点放在牛尾侧间盘，它只在背伸和侧弯的情况下加载，是更复杂的人类腰椎间盘的一个常用模型。活体动物运动跟踪将与数值模拟相结合，以估计在典型一天的过程中尾部所有圆盘上的多轴载荷大小。显微结构成像将用于量化每个椎间盘中残余应变发展的分布。显微分析将用于比较这些椎间盘之间的组织结构。这项工作的结果将被用来建立针对患者的人类脊柱计算机模型，它将能够确定负载模式的变化，如职业的变化。总之，这些研究将得出负荷和残余应变之间的直接联系，这将使未来针对患者的人类腰椎模型能够预测日常生活活动中的损伤风险。这一奖项反映了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。

Animal subjects are frequently used as substitutes for humans in biomechanics research studies. This is typically justified by low variability between animal subjects, low cost, and high biological similarity across species. While the biology of animal tissues, such as cartilage and ligaments, has been studied extensively, little is often known about the forces acting on them during normal activity. This study will leverage the fact that some animal tissues are subjected to much narrower ranges of loading than those of humans to draw connections between load and tissue structure. This Engineering Research Initiation (ERI) project will examine the loads acting on different discs in the bovine tail throughout the day through a combination of live-animal motion tracking and computer modeling. This work will establish animal models as ideal systems for studying the interplay between mechanics and biology. Results of this research will reduce the societal burden of low back pain by contributing to patient-specific models, which will be able to determine whether a change in load pattern, such as change in occupation. This work will be presented to both adult citizen scientists through the local community-based science café series and to young scientists through an annual university-hosted science and engineering fair.This project is to examine bovine caudal intervertebral discs to understand the relationship between the tissue structure and in-vivo loading history. In-vivo loading had been a critical limitation in the ability to study the process of tissue remodeling in response to load. This study will focus on the bovine caudal intervertebral disc, which is loaded only in dorsal extension and lateral bending and is a frequently used model of the more complexly loaded human lumbar disc. Live-animal motion tracking will be combined with numerical modeling to estimate multi-axial load magnitudes on all discs in the tail over the course of a typical day. Microstructural imaging will be used to quantify the distribution of residual strain development in each disc. Microscopic analysis will be used to compare tissue structure between these discs. The results of this work will be used to build patient-specific computer models of the human spine, which will be able to determine whether a change in load pattern, such as change in occupation. Together, these studies will draw a direct link between load and residual strain, which will enable future patient-specific models of the human lumbar spine with a goal of predicting injury risk from activities of daily living.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.