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

Abstract

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 1 in conjunction with baboon insoluble collagenous bone matrix as carrier (5, 30, and 100 micrograms of hTGF-beta 1/g of matrix). The fourth defect was implanted with collagenous matrix without hTGF-beta 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 1-treated defects, irrespective of the doses used. Histomorphometry of the defect site showed no significant differences between control and hTGF-beta 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 micrograms of hTGF-beta 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 1, in conjunction with collagenous matrix, results in limited chondro-osteogenesis in defects of membranous bone of adult baboons.