Human recombinant transforming growth factor-beta 1 in healing of calvarial bone defects

Bone healing plays an important role in orthognathic and craniofacial surgery. Bone tissue repair and regeneration are regulated by an array of growth and morphogenetic factors. Osteogenesis proceeds through a cascade of molecular and cellular events sequentially coordinated by members of both the bone morphogenetic protein and transforming growth factor-beta (TGF-beta) families. The efficacy of a single application of 2, 5, or 10 mu g of recombinant human (rh) TGF-beta 1 to promote bone regeneration in 5-mm experimental calvarial defects of adult male rats was assessed histologically and histomorphometrically. The histomorphometric results of the experimental site were compared with those of the contralateral control side. Dose-group comparisons were also performed. None of the control and experimental bone defects demonstrated complete bone closure. Limited bone regeneration was found close to the margins of the defects. A statistically significant difference in volume fraction composition (bone, osteoid, and soft tissue) was found between the 5- and 10-mu g rhTGF-beta 1-implanted and control defects. No difference was found in the 2-mu g rhTGF-beta 1-implanted group. The percentage of bone closure was statistically significantly higher in the 5-mu g rhTGF-beta 1-implanted group than in the control group. The present findings indicate that a single application of different doses of rhTGF-beta 1 does not promote clinically relevant osteogenesis in membranous calvarial bone defects in adult rats.