Acceleration of bone healing process by local application of the resorbable collagen pellet containing basicfibroblast growth factor (FGF-2)

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We performed an animal study to ascertain whether the regeneration of membrane-protected bone defects can be accelerated by the controlled application of basic fibroblast growth factor (FGF-2) using a new drug delivery system. First, we investigated in vitro effects of FGF-2 on the mineralization process in primary cultures of dog growth plate chondrocytes. Chondrocytes were isolated from the growth plates of ribs of 1-week-old dogs. The chondrocytes were maintained at extremely high density (5 x 10^4 cells/well) on collagen-coated 96-well dishes in a-MEM with 10% fetal bovine serum and 50 mug/ml ascorbic acid. Mineralization was initiated between days 20 and 24 ; however, the addition of fibroblast growth factor (FGF)-2 (1.0 ng/ml) suppressed mineralization. Second, we performed in vivo study using beagle dogs. Alveolar bone defects were made surgically in 9 beagle dogs, and FGF-2 was administered using specially made collagen pellets. A pellet containing either 0.15 mug FGF-2 (FGF) or 0 mug FGF-2 (placebo) was placed in the defect or no minipellet was used (control), and bone regeneration was evaluated radiologically, histologically, and histomorphometrically 8 weeks after the operation. X-ray radiographs showed a surprisingly large radiopaque region in FGF sites compared with placebo or control sites. Histologically, mature bone filled the majority of the inner space of the membrane-protected defect in FGF sites. New bone formation was also seen in the control and the placebo sites, however, it filled less than half the area of the defect. Histomorphometrically, the area of regenerated bone in FGF sites was significantly higher than in the other sites (p<0.01). These results demonstrate that the controlled application of FGF-2 accelerates bone regeneration in membrane-protected bone defects.