Abstract
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.
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References
Ackland DC, Moskaljuk A, Hart C, Vee Sin-Lee P, Dimitroulis G (2015) Prosthesis loading after temporomandibular joint replacement surgery: a musculoskeletal modeling study. J Biomech Eng 137(4):041001
Arnold AS, Liu MQ, Schwartz MH, Ounpuu S, Dias LS, Delp SL (2006) Do the hamstrings operate at increased muscle-tendon lengths and velocities after surgical lengthening? J Biomech 39:1498–1506
Barkaoui A, Chamekh A, Merzouki T, Hambli R, Mkaddem A (2014) Multiscale approach including microfibril scale to assess elastic constants of cortical bone based on neural network computation and homogenization method. Int J Numer Method Biomed Eng. 30(3):318–338
Buehler MJ, Genin GM (2016) Integrated multiscale biomaterials experiment and modelling: a perspective. Interface Focus 6:20150098. doi:10.1098/rsfs.2015.0044
Bujtár P, Sándor GKB, Bojtos A, Szűcs A, Barabás I (2010) Finite element analysis of the human mandible at 3 different stages of life. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 110(3):301–309
Cha JY, Pereira MD, Smith AA, Houschyar KS, Yin X, Mouraret S, Brunski JB, Helms JA (2015) Multiscale analyses of the bone-implant interface. J Dent Res 94(3):482–490
Christen P, Ito K, Ellouz R, Boutroy S, Sornay-Rendu E, Chapurlat RD, van Rietbergen B (2014) Bone remodelling in humans is load-driven but not lazy. Nat Commun 5:4855
Colloca M, Blanchard R, Hellmich C, Ito K, van Rietbergen B (2014) A multiscale analytical approach for bone remodeling simulations: linking scales from collagen to trabeculae. Bone 64:303–313
Dao TT (2016) Enhanced musculoskeletal modeling for prediction of intervertebral disc stress within annulus fibrosus and nucleus pulposus regions during flexion movement. J Med Biol Eng 36(4):583–593
Dao TT (2015) Musculoskeletal simulation for assessment of effect of movement-based structure-modifying treatment strategies. J Comput Med. Article ID 939480
Dao TT, Ho Ba Tho MC (2014) Biomechanics of the musculoskeletal system: modelling of data uncertainty and knowledge. Wiley Publisher, Hermes Penton Ltd, London
Dao TT, Ho Ba Tho MC (2015) Uncertainty modeling and propagation in musculoskeletal modeling. Adv Intell Syst Comput 326:567–576
Dao TT, Pouletaut P (2015) A Hertzian Integrated Contact model of the total knee replacement implant for the estimation of joint contact forces. J Comput Med. Article ID 945379
Dao TT, Tho HB (2015) Assessment of parameter uncertainty in rigid musculoskeletal simulation using a probabilistic approach. J Musculoskelet Res 18(3):1550013
Dao TT, Marin F, Pouletaut P, Aufaure P, Charleux F, Ho Ba Tho MC (2012) Estimation of accuracy of patient specific musculoskeletal modeling: case study on a post polio residual paralysis subject. Comput Method Biomech Biomed Eng 15(7):745–751
Dao TT, Pouletaut P, Charleux F, Lazáry Á, Eltes P, Varga PP, Tho MCHB (2015) Multimodal Medical Imaging (CT and Dynamic MRI) Data and computer-graphics multi-physical model for the estimation of patient specific lumbar spine muscle forces. Data Knowl Eng 96–97:3–18
Delp SL, Anderson FC, Arnold AS, Loan P, Habib A, John CT, Guendelman E, Thelan DG (2007) OpenSim: open-source software to create and analyze dynamic simulations of movement. IEEE Trans Biomed Eng 55:1940–1950
Fang F, Lake SP (2016) Modelling approaches for evaluating multiscale tendon mechanics. Interf Focus 6:20150044. doi:10.1098/rsfs.2015.0044
Fernandez J, Zhang J, Heidlauf T, Sartori M, Besier T, Röhrle O, Lloyd D (2016) Multiscale musculoskeletal modelling, data-model fusion and electromyography-informed modelling. Interf Focus 6(2):20150084
Finocchietti S, Takahashi K, Okada K, Watanabe Y, Graven-Nielsen T, Mizumura K (2013) Deformation and pressure propagation in deep tissue during mechanical painful pressure stimulation. Med Biol Eng Compu 51(1):113–122
Geers MGD, Kouznetsova VG, Brekelmans WAM (2010) Multi-scale computational homogenization: trends and challenges. J Comput Appl Math 234(7):2175–2182
Gefen A (2011) Patient-specific modeling in tomorrow’s medicine. Springer, Berlin
Gonçalves Coelho P, Rui Fernandes P, Carriço Rodrigues H (2011) Multiscale modeling of bone tissue with surface and permeability control. J Biomech 44(2):321–329
Grignard A, Taillandier B, Gaudou B, Vo DA, Huynh NQ, Drogoul A (2013) GAMA, 1.6: advancing the art of complex agent-based modeling and simulation. Lect Notes Comput Sci 8291:117–131
Halloran JP, Sibole S, van Donkelaar CC, van Turnhout MC, Oomens CW, Weiss JA, Guilak F, Erdemir A (2012) Multiscale mechanics of articular cartilage: potentials and challenges of coupling musculoskeletal, joint, and microscale computational models. Ann Biomed Eng 40(11):2456–2474
Halloran JP, Sibole S, van Donkelaar CC, van Turnhout MC, Oomens CW, Weiss JA, Guilak F, Erdemir A (2012) Multiscale mechanics of articular cartilage: potentials and challenges of coupling musculoskeletal, joint, and microscale computational models. Ann Biomed Eng 40(11):2456–2474
Hambli R (2014) Connecting mechanics and bone cell activities in the bone remodeling process: an integrated finite element modeling front. Bioeng Biotechnol. doi:10.3389/fbioe.2014.00006
Hamed E, Novitskaya E, Li J, Jasiuk I, McKittrick J (2015) Experimentally-based multiscale model of the elastic moduli of bovine trabecular bone and its constituents. Mater Sci Eng C Mater Biol Appl 54:207–216
Hannam AG, Stavness I, Lloyd JE, Fels S (2008) A dynamic model of jaw and hyoid biomechanics during chewing. J Biomech 41(5):1069–1076
Helzlsouer KJ (1993) Markers of disease. Sci 262:1082–1083
Hernández JA, Oliver J, Huespe AE, Caicedo MA, Cante JC (2014) High-performance model reduction techniques in computational multiscale homogenization. Comput Methods Appl Mech Eng 276:149–189
Ho H, Suresh V, Kang W, Cooling MT, Watton PN, Hunter PJ (2011) Multiscale modeling of intracranial aneurysms: cell signaling, hemodynamics, and remodeling. IEEE Trans Biomed Eng 58(10):2974–2977
Hughes RE, An KN (1997) Monte Carlo simulation of a planar shoulder model. Med Biol Eng Comput 35(5):544–548
Ilic S, Hackl K, Gilbert R (2010) Application of the multiscale FEM to the modeling of cancellous bone. Biomech Model Mechanobiol 9(1):87–102
Jonkers I, Sauwen N, Lenaerts G, Mulier M, Van der Perre G, Jaecques S (2008) Relation between subject-specific hip joint loading, stress distribution in the proximal femur and bone mineral density changes after total hip replacement. J Biomech 41(16):3405–3413
Kapela A, Tsoukias NM (2011) Multiscale FEM modeling of vascular tone: from membrane currents to vessel mechanics. IEEE Trans Biomed Eng 58(12):3456–3459
Langenbach GEJ, Hannam AG (1999) The role of passive muscle tensions in a three-dimensional dynamic model of the human jaw. Arch Oral Biol 44:557–573
Liu G, Qutub AA, Vempati P, Mac Gabhann F, Popel AS (2011) Module-based multiscale simulation of angiogenesis in skeletal muscle. Theor Biol Med Model 8:6
Makssoud HE, Guiraud D, Poignet P, Hayashibe M, Wieber PB, Yoshida K, Azevedo-Coste C (2011) Multiscale modeling of skeletal muscle properties and experimental validations in isometric conditions. Biol Cybern 105(2):121–138
Orthopaedics GK (2014) Joint effort. Nature 515:S170–S171
Ozada N (2016) Biomechanical model of knee collateral ligament injury with six degrees of freedom. Med Biol Eng Comput 54(5):821–830
Podshivalov L, Fischer A, Bar-Yoseph PZ (2001) 3D hierarchical geometric modeling and multiscale FE analysis as a base for individualized medical diagnosis of bone structure. Bone 48(4):693–703
Qasim M, Farinella G, Zhang J, Li X, Yang L, Eastell R, Viceconti M (2016) Patient-specific finite element estimated femur strength as a predictor of the risk of hip fracture: the effect of methodological determinants. Osteoporos Int 27(9):2815–2822
Riggs MM, Peterson MC, Gastonguay MR (2012) Multiscale physiology-based modeling of mineral bone disorder in patients with impaired kidney function. J Clin Pharmacol 52(1):45S–53S
Röhrle O, Davidson JB, Pullan AJ (2012) A physiologically based, multi-scale model of skeletal muscle structure and function. Front Physiol 3:358
Sanz-Herrera JA, García-Aznar JM, Doblaré M (2009) On scaffold designing for bone regeneration: a computational multiscale approach. Acta Biomater 5(1):219–229
Sharafi S, Li G (2015) A multiscale approach for modeling actuation response of polymeric artificial muscles. Soft Matter 11(19):3833–3843
Tawhai M, Bischoff J, Einstein D, Erdemir A, Guess T, Reinbolt J (2009) Multiscale modeling in computational biomechanics: determining computational priorities and addressing current challenges. IEEE Eng Med Biol Mag 28(3):41–49
Tho HBMC, Mazeran PE, El Kirat K, Bensamoun S (2012) Multiscale characterization of human cortical bone. Comput Model Eng Sci 87(6):557–577
Vadgama P (1992) Opportunities for the cellular approach in biomedical engineering. Med Biol Eng Comput 30(4):CE2–CE7
Viceconti M (2012) Multiscale modeling of the skeletal system. Cambridge University Press, Cambridge
Viceconti M (2015) Biomechanics-based in silico medicine: the manifesto of a new science. J Biomech 48(2):193–194
Viceconti M, Taddei F, Cristofolini L, Martelli S, Falcinelli C, Schileo E (2012) Are spontaneous fractures possible? An example of clinical application for personalised, multiscale neuro-musculo-skeletal modelling. J Biomech 45(3):421–426
Wang L, Zhu Y, Li H, Liu W, Magnin IE (2012) Multiscale modeling and simulation of the cardiac fiber architecture for DMRI. IEEE Trans Biomed Eng 59(1):16–19
Webster D, Müller R (2011) In silico models of bone remodeling from macro to nano–from organ to cell. Wiley Interdiscip Rev Syst Biol Med. 3(2):241–251
Zöllner AM, Pok JM, McWalter EJ, Gold GE, Kuhl E (2015) On high heels and short muscles: a multiscale model for sarcomere loss in the gastrocnemius muscle. J Theor Biol 65:301–310
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The author would like to thank P. Pouletaut for his assistance in the development of finite element model of the jaw system.
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Dao, T.T. Advanced computational workflow for the multi-scale modeling of the bone metabolic processes. Med Biol Eng Comput 55, 923–933 (2017). https://doi.org/10.1007/s11517-016-1572-z
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DOI: https://doi.org/10.1007/s11517-016-1572-z