RhBMP-2 and -7 combined with absorbable collagen sponge carrier enhance ectopic bone formation: An in vivo bioassay

Abstract

Abstract Background: Recombinant human bone morphogenetic proteins (rhBMPs) have been characterized especially chondrogenic and osteogenic activity both in vitro and in vivo studies. However, delivery of more than one growth factor by sustained release carrier to orthopedic site has yet been questionable in terms of efficacy and synergism. Objective: Evaluate osteoinductivity and synergistic effect of rhBMP-2 and -7 using absorbable collagen sponge (ACS) carrier system in vivo. Methods: cDNA of BMP-2 and -7 active domains were cloned and expressed in Escherichia coli BL21 StarTM (DE3) using pRSETc expression system. Then, the purified rhBMPs were loaded onto ACS and evaluated by in vivo rat subcutaneous bioassay. Two and eight weeks postoperatively, all treated groups were histologically verified for evidence of new bone formation and neovascularization by hematoxylin-eosin staining and light microscopy. Results: The Wistar rat treated with rhBMP-2 or -7/ACS exhibited new bone formation, compared to ACS control. The group treated with ACS supplemented with both rhBMP-2 and -7 significantly showed the osteoid matrix very well-organized into trabeculae-like structure with significant blood vessel invasion. Conclusion: The osteogenic induction of rhBMPs was combined with ACS carrier in the in vivo bioassay. In addition, the combination of both two potent recombinant osteoinductive cytokines, rhBMP-2 and -7, with ACS carrier demonstrated synergistic effect and might be a more promising and effective choice for therapeutic applications.