Background and objectives : Osteoplastic materials are high demanded in maxillofacial surgery as an important tool for bone defects repair. Development of postgenomic, cellular and gene technologies is the basis for making of advanced osteoplastic materials characterized by pronounced osteoinduction due to inclusion of biologicaly active components, such as growth factors, cells or gene constructions. Considering some limitations of the first two we focused our efforts on making of gene-activated bone graft (GABG).
Methods : We have developed several variants of GABGs consisting of scaffold (collagen/hydroxyapapite and xenogenic deproteinized bone matrix) and DNA plasmids with gene encoding vascular endothelial growth factor (VEGF). These gene constructions have high angiogenic activity critically significant for reparative osteogenesis. We incubated GABGs with cell cultures (multipotent mesenchymal stromal cells) and measured the expression level of VEGF in cultural medium. Control groups were the same cells incubated with scaffolds only and without any materials as well. Also we estimated GABGs efficacy in vivo. We have performed symmetric critical-size (10 mm) defects of both parietal bones of rabbits. GABGs were implanted into right defects, while scaffolds without plasmids – into left ones. In a row of cases two-cassette DNA plasmids additionally consisting of GFP gene were used for GABG making that allowed to detect the cells transfection in vivo. The results were assessed on 15, 30, 45, 60, 90, 120 days by CT scanning, histochemical, immunohistochemical and histomorphometric analyses.
Results : We have shown the increase of VEGF expression by MMSC in case of their incubation with GABGs. Cells transfection in vivo by GABGs plasmids was detected and that resulted to more pronounced angiogenesis and reparative osteogenesis in all time points in experimental groups unlike controls.
Conclusions : GABGs are effective for bone defects repair that allowed us to start the clinical trials.
Key words gene-activated bone graft; plasmid VEGF; osteogenesis