1. Understanding the relationship between interfragmentary movement and callus growth in fracture healing: a novel computational approach
Cameron Wilson1, Nicole Loechel1, Michael Schuetz1,2, Devakar Epari1
1 Institute of Health and Biomedical Innovation, Queensland University of Technology, Brisbane.
2 Princess Alexandra Hospital, Brisbane.

2. Mechano-regulation of fracture healing
Movement at fracture affects healing process.
External
fixator
Less
movement
More
movement:
more callus
[more movement: larger callus, more cartilage, up to hypertrophic non-union; too-rigid fixation: healing response ends before repair complete]
Epari et al., Bone, 2006
Sheep 2 weeks

3. Mechano-regulation of fracture healing
Movement at fracture affects healing process.
More rigid:
smaller callus
More flexible:
larger callus
[more movement: larger callus, more cartilage, up to hypertrophic non-union; too-rigid fixation: healing response ends before repair complete]
Epari et al., Bone, 2006
Sheep 3 weeks

4. Mechano-regulation of fracture healing
Movement at fracture affects healing process.
Callus size, shape & composition all affect mechanical function.
For optimal outcomes, how much stability & when?
[more movement: larger callus, more cartilage, up to hypertrophic non-union; too-rigid fixation: healing response ends before repair complete]

5. Simulation of fracture healing
Pauwels (1940, 1960):
local mechanical conditions determine changes in healing tissue.
Can’t measure directly  simulation.
Carter (1988), Prendergast (1997), Claes (1999):
finite element analyses vs histology  hypothetical quantitative relationships.

6. Simulation of fracture healing
Iterative schemes: test hypothetical relationships.
Callus size? Morphology?
Bone fraction 2w
 4w
miss IFM-size relationship & morphology
Low movement
High movement
Adapted from Stürmer, Unfallchirurgie, 1984
Simon et al., Comput Methods Biomech Biomed Engin , 2011

7. Methods: incorporating growth
Interfragmentary movement
decreases
Growth & inflammatory signals
Greater
stability
Initial haematoma
Cell proliferation,
matrix production
We hypothesised that callus growth is stimulated by diffusible signals, whose production is in turn regulated by mechanical conditions at the fracture site. We proposed that introducing this scheme into computational models would better replicate the observed tissue patterns and the inverse relationship between callus size and fixation stiffness.
We compared healing patterns vs fixation stiffness between a novel computational callus growth model and corresponding experimental data.
Intramembranous ossification in expanded periosteum & endosteum

8. Results: sheep tibial osteotomy models
Elastic modulus
over 4 weeks
Stiff Fixation
Flexible Fixation
Models in which healing progressed within a prescribed callus domain predicted that greater interfragmentary movements would displace early periosteal bone formation further from the fracture. This results from artificially large distortional strains predicted near the fracture edge. While experiments showed increased hard callus size under flexible fixation, this was not reflected in the standard models. Allowing the callus to grow from a thin soft tissue layer, in response to a mechanically stimulated diffusible signal, results in a callus shape and tissue distribution closer to those observed histologically. Importantly, the callus volume increased with increasing interfragmentary movement.

9. Discussion & Conclusions
Faster callus growth with larger movement. 
Callus morphology similar to histology/x-rays. 
Tool to test simple hypothetical relationship between movement & callus development.
Approach reduces dependence on unknown mechanical properties & cellular responses.

10. Ongoing work Predict & compare against experimental results.
Sensitivity analysis & parameter optimisation.
Clinical aim:
Test effects of varying fixation stiffness during healing.

11. Thank-you

12. Simulation of fracture healing
Discrepancy due to presumed callus domain:
Elevated strain from presumed soft tissue
Wilson et al., Biomech Model Mechanobiol, 2015
[predictions vs experiments – path of healing process]
Simon et al., Comput Methods Biomech Biomed Engin , 2011
Adapted from Stürmer, Unfallchirurgie, 1984