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

人体肌肉骨骼系统是一个复杂的非线性系统，具有从全身到细胞水平的时空相互作用。在许多情况下，要从根本上理解这些相互作用，就需要一种跨越多维尺度的综合建模方法，即“多尺度”建模。我的研究计划的长期目标是开发特定于对象的人类肌肉骨骼系统的多尺度模型，以获得对机械生物学过程的基本了解。人类骨骼的形式和功能为探索多尺度建模过程的有效性提供了一个极好的工具；骨骼是一种具有活跃细胞环境的层级结构，它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。我的研究计划的短期目标(即，未来5年)是验证和验证人体骨骼系统不同维度尺度上的各个子模型，最终目标是预测全身运动导致的细胞水平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的方法，我的学生和我将：1)使用特定于受试者的肌肉骨骼建模来量化施加于骨骼的肌力的敏感度，包括骨骼几何、肌肉起始点和插入点的特定输入，以及肌肉横截面面积和力量的测量，2)验证特定学科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；3)量化组织和细胞水平的骨应变之间的关系，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与机械转导、骨重建和生物组织的功能适应过程有关的假设和问题。这项工作将显著推进生物力学工程领域中用于实验、分析和计算建模查询的技术的现状。肌肉骨骼系统的综合建模迫在眉睫，但实现、验证和确认不同维度尺度上的个别子模型是使特定对象的多尺度建模技术成为有意义的现实的必要第一步。

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.**