The synergetic bone-forming effects of combinations of growth factors expressed by adenovirus vectors on chitosan/collagen scaffolds

Abstract

Supporting and enhancing the regeneration and stability of alveolar bone at dental implant sites is necessary to improve implant integration and stability. In this study chitosan/collagen scaffolds combined with adenoviruses expressing either bone morphogenetic protein 7 (BMP-7), platelet-derived growth factor B (PDGF-B), or a combination of both BMP-7 and PDGF-B, were prepared by a freeze–drying method. The cytotoxicity of the resulting biomaterials, and their potential effects on cell proliferation and differentiation towards an osteoblast phenotype, were studied in an initial in vitro study using human periodontal ligament cells (HPLCs). These in vitro results indicate that the scaffold materials are not cytotoxic, and moreover that scaffolds expressing PDGF-B show a higher proliferation rate, while scaffolds expressing BMP-7 show a stronger differentiation towards the osteoblast phenotype. In a subsequent in vivo study, scaffolds were implanted into surgically induced defects on both sides of the dog mandible. Bone formation, which was evaluated histomorphometrically at 4 and 8 weeks and after sacrificing the animals at 12 weeks, revealed a significant increase in bone formation in scaffolds expressing only BMP-7 and also the combined growth factors, with the highest increase occurring for the scaffold expressing both BMP-7 and PDGF-B. This study demonstrates the promising potential of biomaterial expression of combinations of growth factors such as BMP-7 and PDGF-B for bone regeneration in tissue engineering applications.