Advanced computational workflow for the multi-scale modeling of the bone metabolic processes

Multi-scale modeling of the musculoskeletal system plays an essential role in the deep understanding of complex mechanisms underlying the biological phenomena and processes such as bone metabolic processes. Current multi-scale models suffer from the isolation of sub-models at each anatomical scale. The objective of this present work was to develop a new fully integrated computational workflow for simulating bone metabolic processes at multi-scale levels. Organ-level model employs multi-body dynamics to estimate body boundary and loading conditions from body kinematics. Tissue-level model uses finite element method to estimate the tissue deformation and mechanical loading under body loading conditions. Finally, cell-level model includes bone remodeling mechanism through an agent-based simulation under tissue loading. A case study on the bone remodeling process located on the human jaw was performed and presented. The developed multi-scale model of the human jaw was validated using the literature-based data at each anatomical level. Simulation outcomes fall within the literature-based ranges of values for estimated muscle force, tissue loading and cell dynamics during bone remodeling process. This study opens perspectives for accurately simulating bone metabolic processes using a fully integrated computational workflow leading to a better understanding of the musculoskeletal system function from multiple length scales as well as to provide new informative data for clinical decision support and industrial applications.

[1]  F Marin,et al.  Estimation of accuracy of patient-specific musculoskeletal modelling: case study on a post polio residual paralysis subject , 2012, Computer methods in biomechanics and biomedical engineering.

[2]  Attila Bojtos,et al.  Finite element analysis of the human mandible at 3 different stages of life. , 2010, Oral surgery, oral medicine, oral pathology, oral radiology, and endodontics.

[3]  May Q. Liu,et al.  Do the hamstrings operate at increased muscle-tendon lengths and velocities after surgical lengthening? , 2006, Journal of biomechanics.

[4]  Marco Viceconti.  Multiscale Modeling of the Skeletal System , 2011 .

[5]  Marc R Gastonguay,et al.  Multiscale Physiology‐Based Modeling of Mineral Bone Disorder in Patients With Impaired Kidney Function , 2012, Journal of clinical pharmacology.

[6]  Philippe Pouletaut,et al.  Multimodal medical imaging (CT and dynamic MRI) data and computer-graphics multi-physical model for the estimation of patient specific lumbar spine muscle forces , 2015, Data Knowl. Eng..

[7]  A. Erdemir,et al.  Multiscale modeling in computational biomechanics : determining computational priorities and addressing current challenges , 2017 .

[8]  Markus J Buehler,et al.  One contribution of 19 to a theme issue ‘ Integrated multiscale biomaterials experiment and modelling : towards function and pathology , 2015 .

[9]  I. Jonkers,et al.  Relation between subject-specific hip joint loading, stress distribution in the proximal femur and bone mineral density changes after total hip replacement. , 2008, Journal of biomechanics.

[10]  P. Vadgama,et al.  Opportunities for the cellular approach in biomedical engineering , 1992, Medical and Biological Engineering and Computing.

[11]  Jason P. Halloran,et al.  Multiscale Mechanics of Articular Cartilage: Potentials and Challenges of Coupling Musculoskeletal, Joint, and Microscale Computational Models , 2012, Annals of Biomedical Engineering.

[12]  Guoqiang Li,et al.  A multiscale approach for modeling actuation response of polymeric artificial muscles. , 2015, Soft matter.

[13]  Ridha Hambli,et al.  Connecting Mechanics and Bone Cell Activities in the Bone Remodeling Process: An Integrated Finite Element Modeling , 2014, Front. Bioeng. Biotechnol..

[14]  Ralph Müller,et al.  In silico models of bone remodeling from macro to nano—from organ to cell , 2011, Wiley interdisciplinary reviews. Systems biology and medicine.

[15]  Ridha Hambli,et al.  Multiscale approach including microfibril scale to assess elastic constants of cortical bone based on neural network computation and homogenization method , 2014, International journal for numerical methods in biomedical engineering.

[16]  Peter J. Hunter,et al.  Multiscale Modeling of Intracranial Aneurysms: Cell Signaling, Hemodynamics, and Remodeling , 2011, IEEE Transactions on Biomedical Engineering.

[17]  Helder C. Rodrigues,et al.  Multiscale modeling of bone tissue with surface and permeability control , 2011 .

[18]  Christian Hellmich,et al.  A multiscale analytical approach for bone remodeling simulations: linking scales from collagen to trabeculae. , 2014, Bone.

[19]  Philippe Pouletaut,et al.  A Hertzian Integrated Contact Model of the Total Knee Replacement Implant for the Estimation of Joint Contact Forces , 2015 .

[20]  Fei Fang,et al.  Modelling approaches for evaluating multiscale tendon mechanics , 2016, Interface Focus.

[21]  Benoit Gaudou,et al.  GAMA 1.6: Advancing the Art of Complex Agent-Based Modeling and Simulation , 2013, PRIMA.

[22]  K. An,et al.  Monte Carlo simulation of a planar shoulder model , 1997, Medical and Biological Engineering and Computing.

[23]  O Röhrle,et al.  Multiscale musculoskeletal modelling, data–model fusion and electromyography-informed modelling , 2016, Interface Focus.

[24]  A G Hannam,et al.  A dynamic model of jaw and hyoid biomechanics during chewing. , 2008, Journal of biomechanics.

[25]  Aleksander S Popel,et al.  Module-based multiscale simulation of angiogenesis in skeletal muscle , 2011, Theoretical Biology and Medical Modelling.

[26]  Tien-Tuan Dao,et al.  Uncertainty Modeling and Propagation in Musculoskeletal Modeling , 2014, KSE.

[27]  B. van Rietbergen,et al.  Bone remodelling in humans is load-driven but not lazy , 2014, Nature Communications.

[28]  Marco Viceconti,et al.  Biomechanics-based in silico medicine: the manifesto of a new science. , 2015, Journal of biomechanics.

[29]  K. Gammon.  Orthopaedics: Joint effort , 2014, Nature.

[30]  M. Viceconti,et al.  Patient-specific finite element estimated femur strength as a predictor of the risk of hip fracture: the effect of methodological determinants , 2016, Osteoporosis International.

[31]  Pierre-Brice Wieber,et al.  Multiscale modeling of skeletal muscle properties and experimental validations in isometric conditions , 2011, Biological Cybernetics.

[32]  J. Helms,et al.  Multiscale Analyses of the Bone-implant Interface , 2015, Journal of dental research.

[33]  A. Erdemir,et al.  Multiscale modeling in computational biomechanics , 2009, IEEE Engineering in Medicine and Biology Magazine.

[34]  Ellen Kuhl,et al.  On high heels and short muscles: a multiscale model for sarcomere loss in the gastrocnemius muscle. , 2015, Journal of theoretical biology.

[35]  Ayman Habib,et al.  OpenSim: Open-Source Software to Create and Analyze Dynamic Simulations of Movement , 2007, IEEE Transactions on Biomedical Engineering.

[36]  T. Dao.  Enhanced Musculoskeletal Modeling for Prediction of Intervertebral Disc Stress Within Annulus Fibrosus and Nucleus Pulposus Regions During Flexion Movement , 2016 .

[37]  Adam Kapela,et al.  Multiscale FEM Modeling of Vascular Tone: From Membrane Currents to Vessel Mechanics , 2011, IEEE Transactions on Biomedical Engineering.

[38]  Sara Finocchietti,et al.  Deformation and pressure propagation in deep tissue during mechanical painful pressure stimulation , 2012, Medical & Biological Engineering & Computing.

[39]  J. B. Davidson,et al.  A Physiologically Based, Multi-Scale Model of Skeletal Muscle Structure and Function , 2012, Front. Physio..

[40]  S. Bensamoun,et al.  Multiscale Characterization of Human Cortical Bone , 2012 .

[41]  Amit Gefen.  Patient-specific modeling in tomorrow's medicine , 2012 .

[42]  T. Dao.  Musculoskeletal Simulation for Assessment of Effect of Movement-Based Structure-Modifying Treatment Strategies , 2015 .

[43]  Tien Tuan Dao,et al.  ASSESSMENT OF PARAMETER UNCERTAINTY IN RIGID MUSCULOSKELETAL SIMULATION USING A PROBABILISTIC APPROACH , 2015 .

[44]  I. Jasiuk,et al.  Experimentally-based multiscale model of the elastic moduli of bovine trabecular bone and its constituents. , 2015, Materials science & engineering. C, Materials for biological applications.

[45]  V. G. Kouznetsova,et al.  Multi-scale computational homogenization: Trends and challenges , 2010, J. Comput. Appl. Math..

[46]  J M García-Aznar,et al.  On scaffold designing for bone regeneration: A computational multiscale approach. , 2009, Acta biomaterialia.

[47]  T. Dao,et al.  Biomechanics of the Musculoskeletal System , 2014 .

[48]  Marco Viceconti,et al.  Are spontaneous fractures possible? An example of clinical application for personalised, multiscale neuro-musculo-skeletal modelling. , 2012, Journal of biomechanics.

[49]  A. Huespe,et al.  High-performance model reduction techniques in computational multiscale homogenization , 2014 .

[50]  L Podshivalov,et al.  3D hierarchical geometric modeling and multiscale FE analysis as a base for individualized medical diagnosis of bone structure. , 2011, Bone.

[51]  Neriman Ozada.  Biomechanical model of knee collateral ligament injury with six degrees of freedom , 2015, Medical & Biological Engineering & Computing.

[52]  G. Langenbach,et al.  The role of passive muscle tensions in a three-dimensional dynamic model of the human jaw. , 1999, Archives of oral biology.

[53]  Isabelle E. Magnin,et al.  Multiscale Modeling and Simulation of the Cardiac Fiber Architecture for DMRI , 2012, IEEE Transactions on Biomedical Engineering.

[54]  R. Gilbert,et al.  Application of the multiscale FEM to the modeling of cancellous bone , 2010, Biomechanics and modeling in mechanobiology.

[55]  Prosthesis loading after temporomandibular joint replacement surgery: a musculoskeletal modeling study. , 2015, Journal of biomechanical engineering.