Influence of high-frequency cyclical stimulation on the bone fracture-healing process: mathematical and experimental models

Abstract

Mechanical stimulation affects the evolution of healthy and fractured bone. However, the effect of applying cyclical mechanical stimuli on bone healing has not yet been fully clarified. The aim of the present study was to determine the influence of a highfrequency and low-magnitude cyclical displacement of the fractured fragments on the bone-healing process. This subject is studied experimentally and computationally for a sheep long bone. On the one hand, the mathematical computational study indicates that mechanical stimulation at high frequencies can stimulate and accelerate the process of chondrogenesis and endochondral ossification and consequently the bony union of the fracture. This is probably achieved by the interstitial fluid flow, which can move nutrients and waste from one place to another in the callus. This movement of fluid modifies the mechanical stimulus on the cells attached to the extracellular matrix. On the other hand, the experimental study was carried out using two sheep groups. In the first group, static fixators were implanted, while, in the second one, identical devices were used, but with an additional vibrator. This vibrator allowed a cyclic displacement with low magnitude and high frequency (LMHF) to be applied to the fractured zone every day; the frequency of stimulation was chosen from mechano-biological model predictions. Analysing the results obtained for the control and stimulated groups, we observed improvements in the bone-healing process in the stimulated group. Therefore, in this study, we show the potential of computer mechano-biological models to guide and define better mechanical conditions for experiments in order to improve bone fracture healing. In fact, both experimental and computational studies indicated improvements in the healing process in the LMHF mechanically stimulated fractures. In both studies, these improvements could be associated with the promotion of endochondral ossification and an increase in the rate of cell proliferation and tissue synthesis.

Recent developments on intramedullary nailing: a biomechanical perspective

“…In a study developed by González‐Torres et al. , a finite‐element model of a sheep tibia metatarsus fracture allowed the conclusion that the change in the frequency of the external mechanical stimulus directly affects the interstitial fluid flow velocity in the fracture callus. Goodship et al .…”

“…37,38 However, very recent studies [38][39][40] have started to demonstrate the positive correlation that underestimated high-frequency, low-magnitude interfragmentary micromotions have on the rate and quality of bone fracture healing. According to Gómez-Benito et al, 41 these stimuli may be associated with the promotion of endochondral ossification and an increase in the rate of cell proliferation and tissue synthesis. Although several studies support this concept, it has not yet been fully clarified.…”

“…The importance of frequency value in the mechanical stimulus was also considered. In a study developed by González-Torres et al, 41 a finite-element model of a sheep tibia metatarsus fracture allowed the conclusion that the change in the frequency of the external mechanical stimulus directly affects the interstitial fluid flow velocity in the fracture callus. Goodship et al 38 reinforced the idea that mechanical stimuli do not need to be large to positively influence the fracture-healing process.…”

Computational Modelling of Wound Healing Insights to Develop New Treatments

“…On the other hand, the use of in silico models offers a wide (and cheap) spectrum for analyses. Consequently, it is called to play a prominent role in the design of new treatments, due to its intrinsic capacity to isolate single factors [18].…”

Towards the virtual physiological human: mathematical and computational case studies

“…Burrowes et al [12] demonstrate, via computational simulation of patient-derived vascular occlusions in a model of the pulmonary circulation, that mechanical obstruction alone is not sufficient to cause pulmonary arterial hypertension, additional downstream occlusion being needed to increase pressures significantly. The study by Gómez-Benito et al [13] is aimed at determining the influence of high-frequency, low-amplitude cyclical stimulation on the bonehealing process. Combining experiments and predictions of a previously published mechano-biological model, the authors propose the design of a new bone-healing treatment.…”