Osteogenic potential of recombinant human bone morphogenetic protein-9/absorbable collagen sponge (rhBMP-9/ACS) in rat critical size calvarial defects

Toshiaki Nakamura, Yoshinori Shirakata, Yukiya Shinohara, Richard J. Miron, Kirara Furue, Kazuyuki Noguchi

It has been reported that bone morphogenetic protein (BMP)-9 has potent osteoinductive properties among the BMP family by adenovirus-transfection experiments. We very recently reported that absorbable collagen sponge (ACS) as a carrier for recombinant human (rh) BMP-9, compared with chitosan sponge, was suitable for inducing bone healing/regeneration by BMP-9 in a rat calvarial defect model. The aim of this study was to evaluate different doses of rhBMP-9/ACS on new bone formation in rat critical size calvarial defects. Bilateral calvarial defects (n = 32) were surgically created in 16 wistar rats and randomly filled with one of the following materials: (1) absorbable collagen sponge (ACS) alone; (2) 1 μg-rhBMP-9/ACS (L-rhBMP-9/ACS); (3) 5 μg-rhBMP-9/ACS (H-rhBMP-9/ACS); and (4) blank defects (control). The animals were sacrificed 8 weeks postsurgery for radiographic and histomorphometric analyses. Bone volume and defect closure were statistically higher in the rhBMP-9/ACS-implanted (L-rhBMP-9/ACS and H-rhBMP-9/ACS) groups when compared with ACS-alone group (p < 0.05). Furthermore, defects filled with H-rhBMP-9/ACS showed the highest levels of newly formed bone area (NBA) and NBA/total defect area among all groups. No significant differences in any of the radiographic and histometric parameters could be observed between both concentrations of rhBMP-9. Within the limits of this study, it can be concluded that rhBMP-9/ACS-induced bone formation can be reached with as little as 1 μg/site in rat critical size calvarial defects. RhBMP-9 could be a potential therapeutic growth factor for future bone regenerative procedures.