Abstract
Increasingly, the rat femoral fracture model is being used for preclinical investigations of fracture healing, however, the effect of gap size and its influence on mechanobiology is not well understood. We aimed to evaluate the influence of osteotomy gap on osteotomy healing between the previously published extremes of guaranteed union (0.5 mm) and non-union (3 mm) using this model.A femoral osteotomy in 12–14 week old female Wistar rats was stabilised with a micro fixator (titanium blocks, carbon fiber bars) with an osteotomy gap of 1.0 mm (n = 5), 1.5 mm (n = 7), 2.0 mm (n = 6). After five weeks, the left femur was retrieved. The osteotomy gap was scanned using X-ray microtomography and then histologically evaluated. The radiographic union rate (complete mineralised bone bridging across the osteotomy) was three times higher for the 1.0 mm than the 2.0 mm gap. The 1.0 mm gap had the largest callus (0.069μm3) and bone volume (0.035μm3). Callus and bone volume were approximately 50% smaller within the 2.0 mm gap.Using cadaveric rat femurs stabilised with the external fixator, day 0 mechanical assessment of construct stiffness was calculated on materials testing machine displacement vs load output. The construct stiffness for the 1.0, 1.5 and 2.0 mm gaps was 32.6 ± 5.4, 32.5 ± 2.4, and 32.4 ± 8.3 N/mm (p = 0.779). Interfragmentary strain (IFS) was calculated using the change in osteotomy gap displacement as measured using microstrain miniature differential reluctance transducer spanning the osteotomy gap. Increasing the gap size significantly reduced the IFS (p = 0.013). The mean ‘day 0’ IFS for the 1.0, 1.5 and 2.0 mm gaps were 11.2 ± 1.3, 8.4 ± 1.5 and 6.1 ± 1.2% respectively.A 1.5 mm gap resulted in a delayed fracture healing by 5 weeks and may represent a useful test environment for fracture healing therapy. Increasing gap size did not affect construct stiffness, but did reduce the ‘day 0’ IFS, with a doubling of non-union and halving of bone volume measured between 1.0 and 2.0 mm gaps.
Highlights
Pre-clinical experimental studies frequently use delayed or nonunion models to evaluate a therapy (Garcia et al, 2013)
Studies investigating fracture biology and mechanics have been dominated by large animal models, typically sheep and goats, the use rodent models has significantly increased to nearly 50% of all fracture studies over the last two decades (Garcia et al, 2013), and the rat is used for around one third of all in vivo fracture studies (Mills and Simpson, 2012)
This study showed a 1 mm gap leading to a predominance of union and the 2 mm resulting in a delayed union with an atrophic appearance, indicating non-union, but our study duration was not of sufficient length for an unequivocal definition
Summary
Pre-clinical experimental studies frequently use delayed or nonunion models to evaluate a therapy (Garcia et al, 2013). These are typically created by either mechanical instability, damaging the vascular supply or introducing material to prevent bridging (Mills and Simpson, 2012). Researchers have used defects of up to 8 mm and as low as 0.5 mm in rat fracture studies (Garcia et al, 2013; Mills and Simpson, 2012)
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