Background: The healing period of bone-implant osseointegration usually varies from 3 to 6 months or even longer. Failure may occur during this time. This study aimed to investigate whether osseointegration of dental implants can be enhanced by the combination of growth factors.

Methods: Sixty-four implants were coated with polylactic acid and divided into four groups. Group I was applied with 1.0 mg recombinant human bone morphogenetic protein-2 (rhBMP-2) and 200 μg recombinant human basic fibroblast growth factor (rhbFGF), group II with 1.0 mg rhBMP-2 and 250 μg recombinant human insulin-like growth factor-I (rhIGF-I), group III with 1.0 mg rhBMP-2, and group IV without growth factors as control. In total, 16 rabbits were used, and two osteotomies were drilled on each side of the femur, in which four different groups were randomly placed. Four weeks after implanting, 20 mg calcein green/kg body weight was administered intravenously, and 8 weeks after implanting, 20 mg alizarin/kg body weight was administered intravenously. Twelve weeks after implanting, the animals were sacrificed. The block of bone with implants was embedded in methylmethacrylate and sectioned, and the percentage of new bone surrounding the implant was analyzed by confocal laser scanning microscopy.

Results: There was a statistical difference in bone formation between rhBMP-2–applied groups and the non-applied group at 4 or 8 weeks, and no significant difference between groups I and II (although bone formation in group II was greater than that in group I at 4 weeks). The bone formation in group II was greater than that in group III at 4 or 8 weeks. The formed bone in group I was also greater than the one in group III at 8 weeks, but there was no difference at 4 weeks.

Conclusions: rhBMP-2 could increase new bone formation, and it acted synergistically with rhbFGF and rhIGF-I to improve bone-implant osseointegration. The combination of rhBMP-2 and rhbFGF (group 1) showed faster growth of new bone than other groups at 8 months.