Simulation of fracture healing in the tibia: Mechanoregulation of cell activity using a lattice modeling approach

Byrne, Danielle; Lacroix, Damien; Prendergast, Patrick J.

doi:10.1002/jor.21362

Cited by 91 publications

(74 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In this study, the initial tissue differentiation pattern was predicted based on the mechanoregulation theory of Prendergast et al (1997), which has been widely used in modelling of bone fracture healing Kelly and Prendergast 2005;Isaksson et al 2006;Pérez and Prendergast 2007;Andreykiv et al 2008;Isaksson et al 2008;Nagel and Kelly 2010;Byrne et al 2011). In this theory, it is assumed that the octahedral shear strain and the interstitial fluid velocity relative to solid are two critical parameters that govern the process of tissue differentiation.…”

Section: Tissue Differentiation In the Early Stage Of Healingmentioning

confidence: 99%

Computational simulation of the early stage of bone healing under different configurations of locking compression plates

Miramini

Zhang

Richardson

et al. 2013

Computer Methods in Biomechanics and Biomedical Engineering

View full text Add to dashboard Cite

Flexible fixation or the so-called 'biological fixation' has been shown to encourage the formation of fracture callus, leading to better healing outcomes. However, the nature of the relationship between the degree of mechanical stability provided by a flexible fixation and the optimal healing outcomes has not been fully understood. In this study, we have developed a validated quantitative model to predict how cells in fracture callus might respond to change in their mechanical microenvironment due to different configurations of locking compression plate (LCP) in clinical practice, particularly in the early stage of healing. The model predicts that increasing flexibility of the LCP by changing the bone-plate distance (BPD) or the plate working length (WL) could enhance interfragmentary strain in the presence of a relatively large gap size (> 3 mm). Furthermore, conventional LCP normally results in asymmetric tissue development during early stage of callus formation, and the increase of BPD or WL is insufficient to alleviate this problem.

show abstract

Section: Tissue Differentiation In the Early Stage Of Healingmentioning

confidence: 99%

Computational simulation of the early stage of bone healing under different configurations of locking compression plates

Miramini

Zhang

Richardson

et al. 2013

Computer Methods in Biomechanics and Biomedical Engineering

View full text Add to dashboard Cite

show abstract

“…Several models [1][2][3][4][5] are based on the tissue differentiation hypotheses proposed by Pauwels [6] which were refined by Carter et al [7] and Claes & Heigele [8] using distortional strain and dilatational strain (which is directly related to hydrostatic pressure [5]) as the determining stimuli for tissue differentiation and development. By contrast, other models [9][10][11][12][13][14][15] use a linear combination of distortional strain and fluid velocity as determining stimulus, as characterized by the hypothesis of Prendergast et al [16]. Furthermore, Garcia-Aznar et al [17,18] use only the distortional strain as stimulus.…”

Section: Introductionmentioning

confidence: 99%

Prediction of fracture healing under axial loading, shear loading and bending is possible using distortional and dilatational strains as determining mechanical stimuli

Steiner

Claes

Ignatius

et al. 2013

J. R. Soc. Interface.

View full text Add to dashboard Cite

Numerical models of secondary fracture healing are based on mechanoregulatory algorithms that use distortional strain alone or in combination with either dilatational strain or fluid velocity as determining stimuli for tissue differentiation and development. Comparison of these algorithms has previously suggested that healing processes under torsional rotational loading can only be properly simulated by considering fluid velocity and deviatoric strain as the regulatory stimuli. We hypothesize that sufficient calibration on uncertain input parameters will enhance our existing model, which uses distortional and dilatational strains as determining stimuli, to properly simulate fracture healing under various loading conditions including also torsional rotation. Therefore, we minimized the difference between numerically simulated and experimentally measured courses of interfragmentary movements of two axial compressive cases and two shear load cases (torsional and translational) by varying several input parameter values within their predefined bounds. The calibrated model was then qualitatively evaluated on the ability to predict physiological changes of spatial and temporal tissue distributions, based on respective in vivo data. Finally, we corroborated the model on five additional axial compressive and one asymmetrical bending load case. We conclude that our model, using distortional and dilatational strains as determining stimuli, is able to simulate fracture-healing processes not only under axial compression and torsional rotation but also under translational shear and asymmetrical bending loading conditions.

show abstract

“…All finite elements were cubic with side length of 0.1mm giving each lattice point a spacing of 10 μm. Cell migration was implemented as a stochastic process by filling the allotted new cell position and vacating the previously filled position using random walk theory (Perez and Prendergast 2007;Byrne et al 2011). Each cell attempted to migrate randomly into one of the adjoining lattice position.…”

Section: Cell Migration and Proliferationmentioning

confidence: 99%

Substrate stiffness and oxygen availability as regulators of mesenchymal stem cell differentiation within a mechanically loaded bone chamber

Burke

Khayyeri

Kelly

2014

Biomech Model Mechanobiol

View full text Add to dashboard Cite

Mechanical stimuli such as tissue deformation and fluid flow are often implicated as regulators of mesenchymal stem cell (MSC) differentiation during regenerative events in vivo. However, in vitro studies have identified several other physical and biochemical environmental cues, such as substrate stiffness and oxygen availability, as key regulators of stem cell fate. Hypotheses for how MSC differentiation is regulated in vivo can be either corroborated or rejected based on the ability of in silico models to accurately predict spatial and temporal patterns of tissue differentiation observed experimentally. The goal of this study was to employ a previously developed computational framework to test the hypothesis that substrate stiffness and oxygen availability regulate stem cell differentiation during tissue regeneration within an implanted bone chamber. To enable a prediction of the oxygen levels within the bone chamber, a lattice model of angiogenesis was implemented where blood vessel progression was dependent on the local mechanical environment. The model successfully predicted key aspects of MSC differentiation, including the correct spatial development of bone, marrow and fibrous tissue within the unloaded bone chamber. The model also successfully predicted chondrogenesis within the chamber upon the application of mechanical loading. This study provides further support for the hypothesis that substrate stiffness and oxygen availability regulate stem cell differentiation in vivo. These simulations also highlight the indirect role that mechanics may play in regulating MSC fate by inhibiting blood vessel progression and hence disrupting oxygen availability within regenerating tissues.

show abstract

Simulation of fracture healing in the tibia: Mechanoregulation of cell activity using a lattice modeling approach

Cited by 91 publications

References 42 publications

Computational simulation of the early stage of bone healing under different configurations of locking compression plates

Computational simulation of the early stage of bone healing under different configurations of locking compression plates

Prediction of fracture healing under axial loading, shear loading and bending is possible using distortional and dilatational strains as determining mechanical stimuli

Substrate stiffness and oxygen availability as regulators of mesenchymal stem cell differentiation within a mechanically loaded bone chamber

Contact Info

Product

Resources

About