Limited chondro-osteogenesis by recombinant human transforming growth factor- beta sub(1) in calvarial defects of adult baboons (Papio ursinus)

The therapeutic utility of a single application of recombinant human transforming growth factor- beta (hTGF- beta ) has not been previously tested in large osseous wounds in primates. Sixteen calvarial defects, 25 mm in diameter, were prepared in four adult male baboons ( Papio ursinus). In each animal, three defects were treated with increasing doses of hTGF- beta sub(1) in conjunction with baboon insoluble collagenous bone matrix as carrier (5, 30, and 100 mu g of hTGF- beta sub(1)/g of matrix). The fourth defect was implanted with collagenous matrix without hTGF- beta sub(1) as control. Serial undecalcified sections were prepared from the specimens harvested on day 30. Islands of cartilage and endochondral osteogenesis were found in hTGF- beta sub(1)-treated defects, irrespective of the doses used. Histomorphometry of the defect site showed no significant differences between control and hTGF- beta sub(1)-treated specimens with regard to bone and osteoid volumes. However, analysis of the regenerated tissue in proximity to the defect margins only showed that, on average, greater amounts of bone formed in specimens that were treated with 5 and 30 mu g of hTGF- beta sub(1) when compared with controls. This suggests a possible effect on osteoblastic cells originating from the periosteal and endosteal spaces of the severed calvaria. Overall, however, this difference has no therapeutic implications for the healing of large cranial wounds in primates. The present findings indicate that a single application of hTGF- beta sub(1), in conjunction with collagenous matrix, results in limited chondro-osteogenesis in defects of membranous bone of adult baboons.