Abstract
Background
Large bone defects still challenge the orthopaedic surgeon. Local vascularity at the site of the fracture has an important influence on the healing procedure. Vascular endothelial growth factor (VEGF) and it's receptor (VEGFR2) are potent inducer of angiogenesis during the fracture healing. Aim of the present study was the investigation of critical size fracture (CSF) healing in VEGFR2-luc mice using tailored scaffolds.
Methods
CSFs were performed and stabilised in mouse femur using an external fixator. The fracture was bridged using a synthetic 3D printed scaffold with a defined porosity to promote regeneration. The ß-tricalciumphosphate (ßTCP) and strontium doped ß-tricalciumphosphate (ßTCP+Sr) scaffolds were investigated for their regenerative potential. The expression levels of VEGFR2 could be monitored non-invasively via in vivo bioluminescence imaging for 2 months. After the longitudinal measurements the animals were euthanised for an in depth histological endpoint analysis. The different scaffold induced tissue regeneration was quantified for both, the ßTCP and the ßTCP+Sr group.
Results
Expression levels of VEGFR2 were significantly higher in the ßTCP+Sr group when compared to the ßTCP, control and sham group. Both types of scaffolds significantly enhanced new bone formation when compared to the sham group. The ßTCP+Sr scaffolds showed a significantly greater regenerative potential.
Conclusions
This standardised defect model mimics a clinically relevant situation to study the regenerative effects of biomaterials on bone. Moreover, the rate of regeneration correlates with the VEGFR2 expression levels, what affirms the usability of our method for longitudinal fracture healing studies. As in line with relevant literature, it could be shown that strontium does have an enhancing effect on bone regeneration. Consequently, strontium doped scaffolds might be a useful addition in the surgeon's spectrum of methods.
Level of Evidence
Experimental.
