Fabrication and evaluation of a BMP-2/dexamethasone co-loaded gelatin sponge scaffold for rapid bone regeneration

Improving the osteogenic activity of BMP-2 in vivo has significant clinical application value.In this research,we use a clinical gelatin sponge scaffold loaded with BMP-2 and dexamethasone(Dex)to evaluate the osteogenic activity of dual drugs via ectopic osteogenesis in vivo.We also investigate the mechanism of osteogenesis induced by BMP-2 and Dex with C2C12,a multipotent muscle-derived progenitor cell.The results show that the gelatin scaffold with Dex and BMP-2 can significantly accelerate osteogenesis in vivo.It is indicated that compared with the BMP-2 or Dex alone,100nM of Dex can dramatically enhance the BMP-2-induced alkaline phosphatase activity(ALP),ALP mRNA expression and mineralization.Further studies show that 100nM of Dex can maintain the secondary structure of BMP-2 and facilitate recognition of BMP-2 with its receptors on the surface of C2C12 cells.We also find that in C2C12,Dex has no obvious effect on the BMP-2-induced Smad1/5/8 protein expression and the STAT3-dependent pathway,but Runx2-dependent pathway is involved in the Dex-stimulated osteoblast differentiation of BMP-2 both in vitro and in vivo.Based on these results,a potential mechanism model about the synergistic osteoinductive effect of Dex and BMP-2 in C2C12 cells via Runx2 activation is proposed.This may provide a theoretical basis for the pre-clinical application of Dex and BMP-2 for bone regeneration.