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 growth factor-beta 1 (rhTGF-beta 1) to promote bone regeneration, with or without cellular contribution from the periosteum, was evaluated in transosseous defects. Implantation of rhTGF-beta 1 into 5 mm in diameter "critical size defects" in the rat mandible resulted in a dose-dependent (0.1-20 micrograms/defect) bone bridging at both 12 and 24 days, independent of the type of delivery system [3% methyl cellulose gel, porous CaCO3 particles, or poly(lactide-co-glycolide) beads]. The bridging, however, never exceeded 24% at 12 days or 34% after 24 days. In contrast, when access of cells from the periosteum to the defect was prevented by means of microporous expanded polytetrafluoroethylene barrier membranes (GORE-TEX membrane), rhTGF-beta 1 caused a dose-dependent inhibition of bone regeneration. The bioactivity of the growth factor was confirmed by implantation of 5 or 10 micrograms rhTGF-beta 1 in 12 mm in diameter bicortical defects in rabbit calvaria, which resulted in complete bone healing within 28 days, whereas control defects displayed a bridging of 40%-50%. The findings support the concept, based on in vitro experiments by others, that TGF-beta 1 primarily has a proliferative effect on cells already committed to the osteoblastic lineage, but also imply that TGF-beta 1 may be inhibitory to induction of osteogenic cells in vivo.
Zellin
G
G
Department of Oral Biochemistry, Göteborg University, Sweden. zellin@odontologi.gu.se
Beck
S
S
Hardwick
R
R
Linde
A
A
D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D002146:Bony Callus / Q000187:drug effects / Q000502:physiology; D002455:Cell Division / Q000187:drug effects; D016503:Drug Delivery Systems; D004343:Drug Implants; D017102:Fracture Healing / Q000187:drug effects*; D006801:Humans; D008297:Male; D008334:Mandible / Q000187:drug effects*; D008337:Mandibular Fractures / Q000188:drug therapy*; D008567:Membranes, Artificial; D010006:Osteoblasts / Q000187:drug effects; D010521:Periosteum / Q000166:cytology; D011138:Polytetrafluoroethylene; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000008:administration & dosage / Q000494:pharmacology*
D004343:Drug Implants; D008567:Membranes, Artificial; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D011138:Polytetrafluoroethylene