Tissue differentiation and bone regeneration in an osteotomized mandible: a computational analysis of the latency period

Abstract

Mandibular symphyseal distraction osteogenesis is a common clinical procedure to modify the geometrical shape of the mandible for correcting problems of dental overcrowding and arch shrinkage. In spite of consolidated clinical use, questions remain concerning the optimal latency period and the influence of mastication loading on osteogenesis within the callus prior to the first distraction of the mandible. This work utilized a mechano-regulation model to assess bone regeneration within the callus of an osteotomized mandible. A 3D model of the mandible was reconstructed from CT scan data and meshed using poroelastic finite elements. The stimulus regulating tissue differentiation within the callus was hypothesized to be a function of the strain and fluid flow computed by the finite element model. This model was then used to analyse tissue differentiation during a fifteen day latency period, defined as the time between the day of the osteotomy and the day when the first distraction is given to the device. The following predictions are made: (i) the mastication forces generated during the latency period support osteogenesis in certain regions of the callus, and that during the latency period the percentage of progenitor cells differentiating into osteoblasts increases; (ii) reducing the mastication load by 70% during the latency period increases the number of progenitor cells differentiating into osteoblasts; (iii) the stiffness of new tissue increases at a slower rate on the side of bone callus next to the occlusion of the mandibular ramus which could cause asymmetries in the bone tissue formation with respect to the middle sagittal plane. Although the model predicts that the mastication loading generates such asymmetries, their effects on the spatial distribution of callus mechanical properties are insignificant for typical latency periods used clinically. It is also predicted that a latency period of longer than a week will increase the risk of premature bone union across the callus.

The role of mechanical signals in regulating chondrogenesis and osteogenesis of mesenchymal stem cells

“…Using this mechano-regulation model (Prendergast et al, 1997), it has been possible to predict the spatial and temporal patterns of tissue differentiation during a number of regenerative events such as fracture healing Nagel and Kelly 2009), osteochondral defect repair (Kelly and Prendergast 2005;Kelly and Prendergast 2006) and distraction osteogenesis (Boccaccio et al, 2007;Boccaccio et al, 2008). However even with the use of complex computational models, it is difficult to determine how specific mechanical signals influence MSC differentiation in vivo within the milieu of other regulatory factors that are present.…”

Corroboration of mechanobiological simulations of tissue differentiation in an in vivo bone chamber using a lattice‐modeling approach

“…Both models described tissue regeneration in the chamber qualitatively, but more qualitative and quantitative experimental results are necessary to corroborate the predictive capacities of the models. Although these theories predicted some of the main aspects of tissue regeneration in fracture healing, 5,7-9 tissue engineering, 10,11 bone/implant interfaces, 6,12,13 or distraction osteogenesis, [14][15][16][17] they may be criticized for this lack of corroboration.…”

Mechanobiology of Fracture Healing: Basic Principles and Applications in Orthodontics and Orthopaedics

“…This modelling has been adopted in Prendergast, 2005, 2006). Boccaccio et al (Boccaccio et al, 2007(Boccaccio et al, , 2008a, modelled the cellular dispersal by using the diffusion equation (1) however, they accounted for the fact that MSCs not only require time to differentiate, but that the differentiated cell types require time to synthesise and remodel new tissue. To this purpose, based on the results of Richardson et al (Richardson et al, 1992) who observed an exponential increase in stiffness during tibial fracture healing, they assumed that the Young's modulus of all tissues within the fracture callus increases exponentially with time.…”

“…The spreading of mesenchymal stem cells throughout the bone callus was simulated with the diffusion equation (1) (Boccaccio et al, 2008a). The diffusion coefficient D was set so that the complete cell coverage in the callus is achieved two weeks after the osteotomy.…”