OPPOSITE EFFECTS OF RECOMBINANT HUMAN TRANSFORMING GROWTH-FACTOR-BETA-1 ON BONE REGENERATION IN-VIVO - EFFECTS OF EXCLUSION OF PERIOSTEAL CELLS BY MICROPOROUS MEMBRANE

The efficacy of local delivery of recombinant human transforming growt h factor-beta 1 (rhTGF-beta 1) to promote bone regeneration, with or w ithout cellular contribution from the periosteum, was evaluated in tra nsosseous defects. Implantation of rhTGF-beta 1 into 5 mm in diameter ''critical size defects'' in the rat mandible resulted in a dose-depen dent (0.1-20 mu g/defect) bone bridging at both 12 and 24 days, indepe ndent of the type of delivery system [3% methyl cellulose gel, porous CaCO3 particles, or poly(lactide-co-glycolide) beads]. The bridging, h owever, never exceeded 24% at 12 days or 34% after 21 days. In contras t, when access of cells from the periosteum to the defect was prevente d by means of microporous expanded polytetrafluoroethylene barrier mem branes (GORE-TEX(R) membrane), rhTGF-beta 1 caused a dose-dependent in hibition of bone regeneration. The bioactivity of the growth factor wa s confirmed by implantation of 5 or 10 mu g rhTGF-beta 1 in 12 mm in d iameter bicortical defects in rabbit calvaria, which resulted in compl ete bone healing within 28 days, whereas control defects displayed a b ridging of 40%-50%. The findings support the concept, based on in vitr o experiments by others, that TGF-beta 1 primarily has a proliferative effect on cells already committed to the osteoblastic lineage, but al so imply that TGF-beta 1 may be inhibitory to induction of osteogenic cells in vivo. (C) 1998 by Elsevier Science Inc. All rights reserved.