Knochenregeneration chronischer Knochendefekte der porcinen Maxilla unter kombinierter Freisetzung von rhBMP-2 und rhVEGF-A165 aus PDLLA/CaCO3-composite-Granula

Abstract

The functional aesthetic reconstruction of facial bone defects is one of the challenging aspects in oral and maxillofacial surgery. Free avascular or anastomosed bone grafts are the current gold standard of reconstruction. Current research focuses on alloplastic bone substitute materials, which, analogous to autologous grafts, have osteoconductive, osteoinductive and osteogenic abilities. Carrier materials loaded with growth factors could meet these requirements. The aim of this pilot study was to determine whether the reduced dosage of recombinant human bone morphogenetic protein-2 (rhBMP-2) in combination with recombinant human vascular endothelial growth factor -A165 (rhVEGF-A165) in a slow-release carrier material shows a similar de novo bone formation as the high-dose use of rhBMP-2 in previous studies. For the investigation, a large animal experiment was accomplished with 18 Göttingen mini-pigs, which were subject to critical size defects by extraction of the upper posterior teeth. After the bone defects became chronic, poly-D-L-lactic acid / CaCO3-composite granules, that had been loaded with the respective growth factors, were implanted. A histological and histomorphometric evaluation of the two test (rhBMP-2 and rhBMP-2/rhVEGF-A165) and two control groups (empty defect and unloaded composite granules) was performed after an observation period of four and 13 weeks. The histological examination showed numerous vessels in the augmentation for the combination of rhBMP-2 and rhVEGF-A165. Compared to the control groups, the bone structure appeared more compact in the de novo formed bone and osteoblasts and osteoblasts were found as a sign of increased bone metabolism. Histomorphometrically, de novo bone formation was increased in the two test groups compared to the control groups. Statistically, these results were significant for the rhBMP-2 and rhVEGF-A165 13 week trial groups. It can be concluded that the combination of rhVEGF-A165 and rhBMP-2 with continuous release of the factors can achieve sufficient bone regeneration in critical bone defects.