Multiscale modeling of the skeletal system: whole-body movement to cellular deformation

骨骼系统的多尺度建模：全身运动到细胞变形

• 批准号: RGPIN-2015-04767
• 负责人: Edwards, William
• 金额: $ 1.68万
• 依托单位: University of Calgary
• 依托单位国家: 加拿大
• 项目类别: Discovery Grants Program - Individual
• 财政年份: 2016
• 资助国家: 加拿大
• 起止时间: 2016-01-01 至 2017-12-31
• 项目状态: 已结题
• 来源: https://www.nserc-crsng.gc.ca/ase-oro/Details-Detailles_eng.asp?id=613152
• 关键词: Multiscale; modeling; skeletal; system; whole

The human musculoskeletal system is a complex nonlinear system with spatial and temporal interactions ranging from the whole-body to the cellular level. A fundamental understanding of these interactions in many instances requires an integrative modeling approach that spans multiple dimensional scales, or “multiscale” modeling. The long-term goal of my research program is to develop subject-specific multiscale models of the human musculoskeletal system to gain a fundamental understanding of mechanobiological processes. The form and function of the human skeleton provides an excellent vehicle with which to explore the efficacy of multiscale modeling procedures; bone is a hierarchical structure with an active cellular environment that responds to mechanical stimuli imparted through muscular contraction during activities of daily living. The short-term objective of my research program (i.e., next 5 years) is to verify and validate individual sub-models at different dimensional scales of the human skeletal system with the end goal to predict localized stress and strain fields at the cellular level resulting from whole-body movement. Using a combination of novel experimentation, advanced imaging, and sophisticated modeling, my students and I will: 1) quantify the sensitivity of muscle forces applied to bone using musculoskeletal modeling with subject-specific versus generic inputs of bone geometry, muscle origin and insertion points, and measures of muscle cross-sectional area and strength, 2) validate subject-specific finite element models to predict tissue level bone strain in vivo, and quantify the individual contribution of different muscle groups to strain distribution, and 3) quantify the relationship between tissue and cellular level bone strains in vitro, and determine if osteocyte density and morphology are correlated with strain distribution. My program is designed to challenge current hypotheses and lines of questioning related to mechanotransduction, bone remodeling and the functional adaptation process of biological tissues. This work will significantly advance the current state of technologies used in the fields of biomechanical engineering for experimental, analytical, and computational modeling inquiry. Integrative modeling of the musculoskeletal system is imminent, but the implementation, verification, and validation of individual sub-models across different dimensional scales is the first necessary step to make subject-specific multiscale modeling techniques a meaningful reality.

人体肌肉骨骼系统是一个复杂的非线性系统，从全身到细胞水平都存在时空相互作用。在许多情况下，这些相互作用的基本理解需要一个综合的建模方法，跨越多维尺度，或“多尺度”建模。我的研究计划的长期目标是开发人类肌肉骨骼系统的特定主题的多尺度模型，以获得机械生物学过程的基本理解。 人类骨骼的形式和功能提供了一个很好的工具，探索多尺度建模程序的功效;骨是一个层次结构，具有活跃的细胞环境，对日常生活活动中通过肌肉收缩给予的机械刺激做出反应。我的研究项目的短期目标（即，未来5年）是在人体骨骼系统的不同维度尺度上验证和确认各个子模型，最终目标是预测全身运动导致的细胞水平上的局部应力和应变场。 使用新颖的实验，先进的成像和复杂的建模相结合，我的学生和我将：1）使用肌肉骨骼建模来量化施加到骨骼的肌肉力的灵敏度，其中骨骼几何形状、肌肉起点和插入点的受试者特异性相对于通用输入，以及肌肉横截面积和强度的测量，2）验证受试者特定的有限元模型以预测体内组织水平的骨应变，并量化不同肌肉群对应变分布的个体贡献，和3）在体外定量组织和细胞水平骨应变之间的关系，并确定骨细胞密度和形态是否与应变分布相关。 我的计划旨在挑战目前的假设和有关机械转导，骨重建和生物组织的功能适应过程的质疑线。这项工作将显着推进生物力学工程领域的实验，分析和计算建模调查的技术现状。肌肉骨骼系统的综合建模迫在眉睫，但在不同的维度尺度上实现，验证和确认各个子模型是使特定于主题的多尺度建模技术成为有意义的现实的第一个必要步骤。