Bone Morphogenetic Protein (BMP) 9 Outperforms BMP2 in Osteogenesis and Osseointegration: In Vitro and In Vivo.

OBJECTIVES: This study compared the osteogenic mechanisms and preclinical efficacy of bone morphogenetic protein 9 (BMP9) and BMP2 in vitro and in a beagle peri-implant defect model in vivo. MATERIALS AND METHODS: In vitro, MC3T3-E1 preosteoblasts were treated with BMP2 or BMP9 to assess osteogenic gene expression (Col1, Runx2, Alp, Ocn) by real-time PCR, Smad1/5/9 phosphorylation by western blotting, and osteogenesis by alkaline phosphatase (ALP) and Alizarin Red S staining. In vivo, saddle-type peri-implant defects were created in beagle mandibles and treated with a collagenated xenograft matrix with or without BMP2 or BMP9 (150 μg/site). After 8 weeks, implant stability, micro-CT, histomorphometry, and osseointegration parameters were analyzed. RESULTS: BMP9 significantly enhanced osteogenic gene expression, Smad1/5/9 phosphorylation, ALP activity, and mineralization compared to BMP2. In vivo, BMP9 yielded the highest implant stability values, greater defect fill, and higher bone volume fraction, bone mineral density, and bone-to-implant contact. CONCLUSIONS: BMP9 showed stronger osteoinductive potential than BMP2, resulting in improved bone regeneration and osseointegration. These findings suggest that BMP9 is a promising growth factor for improving dental implant outcomes.