The large bone defects with high risk of delayed bone union and pseudoarthrosis remain significant clinical challenge. Aim of the present study was the investigation of the critical size fracture healing process in transgenic mice using a novel beta-TCP scaffold. The luciferase transgenic mice strains (BALB/C-Tg(NF-kappaB-RE-luc)-Xen) and FVB/N-Tg(Vegfr2-luc)-Xen were used. Critical size fracture on femur was performed and stabilized using external fixation (RISystem). The fracture was bridged with a synthetic scaffold with and without Strontium. In consequence, the expression levels of NF-kappaB and VEGFR2 could be monitored in a longitudinal fashion using the Xenogen imaging system for two months. Animals were euthanized, serial section of femur were prepared, and the fracture sites were histologically examined. Sr reduced inflammation in the early phase of healing (15th days), but it was increased in the late healing stage. The level of VEGFR2 activity increases in the Sr doped beta-TCP group at the 15th day, the luciferase activity starts to decrease in this group and show significantly less activity compared to other groups in the second half. In the group without scaffold a connective tissue formation were observed. In both, beta-TCP and beta-TCP+Sr, the connection of newly formed tissue within integrated canals in scaffold was visible. Tissue formation in beta-TCP+Sr group was significantly higher than in the beta-TCP group, whereas the percentage of osseous tissue in relation to the newly formed tissue was in beta-TCP scaffold much more than in beta-TCP+ Sr groups. This study presents the first data regarding VEGFR2 and NF-kappB and angiogenesis activity profiles during fracture healing. The collected longitudinal data reduces the number of experimental animals in the study. Addition of strontium in scaffolds influenced the inflammation in different stage of the healing. This effect might influence the healing process and may prove to be advantageous for osteoporosis fracture healing.

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.