Nechanobiology IV: Modelling Presentation O-104
AN INTEGRATED MATHEMATICAL MODELLING FRAMEWORK
FOR THE STUDY OF BONE FRACTURE HEALING
Liesbet Geris, Jos Vander Sloten, Hans Van Oosterwyck
Division of Biomechanics and Engineering Design, K.U.Leuven, Belgium
Modelling Framework
Both mechanical and biological factors play an
important role in normal as well as impaired
fracture healing. This study aims to provide a
mathematical framework in which both regulatory
mechanisms are included. To illustrate the added
value of such a framework, a coupled
mechanoregulatory model was proposed (Figure 1-
2). This model was based on the bioregulatory
model of [Geris, 2007], using a simple coupling
between mechanics and biology whereby certain
parameters of the bioregulatory model were made
dependent on local mechanical stimuli. As a first
example, in this study, the proliferation of
osteoblasts and endothelial cells were made
dependent on the local fluid flow [Owan, 1997].
Figure 1: Overview of the implementation of the
coupled mechanobioregulatory model.
Figure 2: (a) Experimental set-up for the semi-
stabilised murine tibia fracture. The arrows
indicate the location of the fracture. (b) Generic
geometric model of the experimental set-up.
Results
Various loading situations, ranging from non-
loading to overloading, were simulated.
Simulations of adverse mechanical circumstances
predicted the formation of avascular nonunions, a
result that was corroborated by various
experimental observations. Treatment strategies
16th ESB Congress, Oral Presentations, Monday 7 July 2008
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were designed, involving the restoration of an
optimal mechanical environment, as well as the
augmentation of the biological potential of the
regeneration site. Stabilisation of the regeneration
site allowed for the resumption of normal healing
processes. Provided that sufficient mechanical
stability was ensured, the use of biological agents
further accelerated the healing process (Figure 3).
Figure 3: Left: temporal evolution (post fracture
days) of the tissue fractions in the callus [%]
(vertical dashed lines indicate stabilisation point at
post fracture day 20). Right: bone matrix density in
the bone chamber at various time points after
stabilisation [× 0.1 g/ml]. Top: stabilisation of the
fracture callus alone. Bottom: combination of
stabilisation and osteogenic growth factor
administration at fracture stabilisation.
Discussion
Thorough sensitivity analyses need to be carried out
to assess the importance of various simplifications
and assumptions made in the course of this study.
The developed mathematical framework is such
that it easily allows for the investigation of
additional mechanical stimuli and for additional
biological processes to be made dependent on these
stimuli. The coupling of both bioregulatory and
mechanoregulatory mechanisms in a single
modelling framework allows for the investigation
of experimentally testable hypotheses and for the
design of clinically relevant treatment strategies.
References
Geris et al, J Theor Biol, In Press, 2007.
Owan et al, Am J Phys, 273:810-815, 1997.
Journal of Biomechanics 41(S1)