LIMITED CHONDRO-OSTEOGENESIS BY RECOMBINANT HUMAN TRANSFORMING GROWTHFACTOR-BETA(1) IN CALVARIAL DEFECTS OF ADULT BABOONS (PAPIO-URSINUS)

The therapeutic utility of a single application of recombinant human t ransforming growth factor-beta (hTGF-beta) has not been previously tes ted in large osseous wounds in primates, Sixteen calvarial defects, 25 mm in diameter, were prepared in four adult male baboons (Papio ursin us), 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 mu g of hTGF-beta(1)/g of matrix), T he fourth defect was implanted with collagenous matrix without hTGF-be ta(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 signi ficant differences between control and hTGF-beta(1)-treated specimens with regard to bone and osteoid volumes. However, analysis of the rege nerated tissue in proximity to the defect margins only showed that, on average, greater amounts of bone formed in specimens that were treate d with 5 and 30 mu g 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, how ever, this difference has no therapeutic implications for the healing of large cranial wounds in primates, The present findings indicate tha t a single application of hTGF-beta(1), in conjunction with collagenou s matrix, results in limited chondro-osteogenesis in defects of membra nous bone of adult baboons.