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

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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.