title: Bone regeneration during distraction osteogenesis: mechano-regulation by shear strain and fluid velocity.
abstract: Corroboration of mechano-regulation algorithms is difficult, partly because repeatable experimental outcomes under a controlled mechanical environment are necessary, but rarely available. In distraction osteogenesis (DO), a controlled displacement is used to regenerate large volumes of new bone, with predictable and reproducible outcomes, allowing to computationally study the potential mechanisms that stimulate bone formation. We hypothesized that mechano-regulation by octahedral shear strain and fluid velocity can predict the spatial and temporal tissue distributions seen during experimental DO. Variations in predicted tissue distributions due to alterations in distraction rate and frequency could then also be studied. An in vivo ovine tibia experiment evaluating bone-segment transport (distraction, 1 mm/day) over an intramedullary nail was used for comparison. A 2D axisymmetric finite element model, with a geometry originating from the experimental data, was created and included into a previously developed model of tissue differentiation. Cells migrated and proliferated into the callus, differentiating into fibroblasts, chondrocytes or osteoblasts, dependent on the biophysical stimuli. Matrix production was modelled with an osmotic swelling model to allow tissues to grow at individual rates. The temporal and spatial tissue distributions predicted by the computational model agreed well with those seen experimentally. In addition, it was observed that decreased distraction rate (0.5 mm/d vs. 0.25 mm/d) increased the overall time needed for complete bone regeneration, whereas increased distraction frequency (0.5 mm/12 h vs. 0.25 mm/6 h) stimulated faster bone regeneration, as found in experimental findings by others. Thus, the algorithm regulated by octahedral shear strain and fluid velocity was able to predict the bone regeneration patterns dependent on distraction rate and frequency during DO.
authors.affiliation: AO Research Institute, Clavadelerstrasse 8, 7270 Davos Platz, Switzerland.
authors.forename: Hanna
authors.initials: H
authors.lastname: Isaksson
authors.forename: Olivier
authors.initials: O
authors.lastname: Comas
authors.forename: Corrinus C
authors.initials: CC
authors.lastname: van Donkelaar
authors.forename: Jesus
authors.initials: J
authors.lastname: Mediavilla
authors.forename: Wouter
authors.initials: W
authors.lastname: Wilson
authors.forename: Rik
authors.initials: R
authors.lastname: Huiskes
authors.forename: Keita
authors.initials: K
authors.lastname: Ito
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000502:physiology*; D008954:Models, Biological; D019857:Osteogenesis, Distraction; D012212:Rheology; D012756:Sheep; D013314:Stress, Mechanical