Low amplitude and high frequency mechanical stimulation does not affect directly cell differentiation during bone healing

Libardo Andrés González Torres, Stephany de Camilo e Alonso, Agnes Batista Meireles


Bone fractures has high incidence and despite its relevance and frequency, some bone healing process features are still unknown. In this work, it is computationally investigated the influence of low amplitude and high frequency mechanical stimulation on cell differentiation during bone healing, using a cell differentiation theory that relates two mechanical variables (strain and flow velocity of interstitial fluid) with the cell fate. For this purpose, a finite element model was developed to study three hypothetical situations, to determine in which proportion external stimulation influences bone healing. Firstly, the mechanical stimulus was computed as 20% of external mechanical stimulus and 80% of the stimulus during gait. Secondly, it was considered 50% external mechanical stimulus and 50% gait stimulus. Finally, it was considered a proportion of 80% external mechanical stimulus and 20% gait stimulus. The results indicated that hypothesis considering high proportions of external stimulation results in unreal delayed healing process and the first hypothetical situation proved to be that which best represents the real process. From the results obtained, it was concluded that external mechanical stimulation does not affected directly cell differentiation during bone healing. Thus, other processes such as flow of oxygen, nutrients or wastes must be considered.


Mechanical Stimulu; Bone Healing; Finite Element Method

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CLAES L, AUGAT P, SCHORLEMMER S, KONRADS C, IGNATIUS A, EHRNTHALLER C. Temporary distraction and compression of a diaphyseal osteotomy accelerates bone healing. J. Orthop. Res. 2008;26:772-777.

CLAES L, GRASS R, SCHMICKAL T, KISSE B, EGGERS C, GERNGROSS H, et al. Monitoring and healing analysis of 100 tibial shaft fractures. Langenbeck’s Archives of Surg. 2002;387:146-152.

CLAES L, HEIGELE, C. Magnitudes of local stress and strain along bony surfaces predict the course and type of fracture healing. J. Biomech. 1999;32:255- 266.

DOBLARÉ M, GARCÍA-AZNAR J, GÓMEZ-BENITO M. Modelling bone tissue fracture and healing: a review, Eng. Frac. Mech. 2004;71:1809-1840.

EBRAHIMI H, RABINOVICH M, VULETA V, ZALCMAN D, SHAH S, DUBOV A, et al. Biomechanical properties of an intact, injured, repaired, and healed femur: An experimental and computational study. J. Mech. Behav. Biomed. Mater. 2012;16:121-135.

EPARI D, DUDA G, THOMPSON M. Mechanobiology of bone healing and regeneration: in vivo models. Proc Inst Mech Eng H. 2010;224:1543-1553.

GARCÍA-AZNAR J, KUIPER J, GÓMEZ-BENITO M, DOBLARÉ M, RICHARDSON J. Computational simulation of fracture healing: Influence of interfragmentary movement on the callus growth. J. Biomech. 2007;40:1467-1476.

GERIS L, GERISCH A, SLOTEN J, WEINER R, OOSTERWYCK H. Angiogenesis in bone fracture healing: A bioregulatory model. J. Theor. Biol. 2008;251:137-158.

GÓMEZ-BENITO M, GARCÍA-AZNAR J, KUIPER J, DOBLARÉ M. Influence of fracture gap size on the pattern of long bone healing: a computational study. J. Theor. Biol. 2005;235:105-119.

GÓMEZ-BENITO M, GONZÁLEZ-TORRES L, REINA-ROMO E, GRASA J, SERAL B, GARCÍA-AZNAR J. Influence of high-frequency cyclical stimulation on the bone fracture-healing process: mathematical and

experimental models. Phil. Trans. 2001;369:4278-4294.

GONZÁLEZ-TORRES L, GÓMEZ-BENITO M, GARCÍA-AZNAR J. Evaluation of residual stresses due to bone callus growth: a computational study. J. Biomech. 2011;44:1782-1787.

GOODSHIP A, KENWRIGHT J. The influence of induced micromovement upon the healing of experimental tibial fractures. J. Bone Joint Surg. 1985;67B:650-655.

GOODSHIP A, LAWES T, RUBIN C. Low-magnitude high-frequency mechanical signals accelerate and augment endochondral bone repair: preliminary evidence of efficacy. J. Orthop. Res. 2009;27:922-930.

ISAKSSON H. Recent advances in mechanobiological modeling of bone regeneration, Mech. Res. Commun. 2012;42:22-31.

LACROIX D, PRENDERGAST P. A mechano-regulation model for tissue differentiation during fracture healing: analysis of gap size and loading. J. Biomech. 2002;35:1163-1171.

MALIZOS K, PAPATHEODOROU L. The healing potential of the periosteum: Molecular aspects. Injury. 2005;36:S13-S19.

MARIEB E. Essentials of Human Anatomy and Physiology. 8th ed. San Francisco. Benjamin Cummings; 2006.

MARSELL R, EINHORN T. The biology of fracture healing. Injury. 2011;42:551- 555.

NIKOLAOU V, STENGEL D, KONINGS P, KONTAKIS G, PETRIDIS G, PETRAKAKIS G, et al. Use of femoral shaft fracture classifi-cation for predicting the risk of associated injuries. J. Orthop. 2011;25:556-559.

PALOMARES K, GLEASON R, MASON Z, CULLINANE D, EINHORN T, GERSTENFELD L, et al. Mechanical Stimulation Alters Tissue Differentiation and Molecular Expression during Bone Healing. J. Orthop. Res.


POKORNÁ P, HEJCMANOVÁ P, HEJCMAN M, PAVLŮ V. Activity time budget patterns of sheep and goats co-grazing on semi-natural species-rich dry grassland.Czech J. Anim. Sci. 2013;58:208-216.

PRENDERGAST P, HUISKES R, SOBALLE K. Biophysical stimulus on cells during tissue differentiation at implant interfaces. J. Biomech. 1997;30:539- 548.

SCHINDELER A, MCDONALD M, BOKKO P, LITTLE D. Bone remodeling during fracture repair: The cellular picture, Semin. Cell Dev. Biol. 2008;19:459-466.

WILSON C, MSCHUETZ M, EPARI D. Effects of strain artefacts arising from a pre-defined callus domain in models of bone healing mechanobiology. Biomech. Model. Mechanobiol. 2015;4:1129-1141.

ZHANG L, RICHARDSON M, MENDIS P. Role of chemical and mechanical stimulus in mediating bone fracture healing. Clin. Exp. Pharmacol. Physiol. 2012;39:706-710.

DOI: https://doi.org/10.5902/2179460X30167

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