Wound healing angiogenesis: indirect stimulation by basic fibroblast growth factor.
Basic fibroblast growth factor (bFGF) was tested for its ability to stimulate angiogenesis in vivo using the rabbit corneal assay. Basic FGF (50-1,000 ng) was incorporated into 10% Hydron, and 50-500 ng of bFGF were incorporated into 10% Elvax. Human serum albumin (HSA) (10 ng) and 50 ng of transforming growth factor-beta (TGF-beta) served as negative and positive controls. Pellets of the polymers containing test compounds were implanted in the rabbit cornea, examined daily, and after 7 days corneal angiogenesis was scored on a graded scale [(-) for no response and +4 for a maximum response]. Histologic analysis of the corneas was performed on days 2 and 7. Basic FGF (50-500 ng) in Hydron failed to stimulate significant angiogenesis, though it did induce angiogenesis accompanied by inflammation at the 1,000-ng dose. Basic FGF in Elvax elicited inflammation-associated +3 to +4 responses at all doses tested. New blood vessels did not form in response to HSA in Hydron or Elvax, while TGF-beta induced +4 angiogenesis accompanied by vigorous inflammation. In vivo release kinetics for bFGF in Hydron and Elvax were compared, and the release of bioactive bFGF from Hydron and Elvax was demonstrated in vitro. These results suggest that the bFGF and Elvax combination incites an inflammatory response which stimulates indirect angiogenesis, while the same concentrations of bFGF delivered in Hydron produced no inflammation or angiogenesis. Although bFGF alone is a potent mitogen for endothelial cells, it does not appear to directly stimulate in vivo angiogenesis.
Department of Surgery, University of Minnesota, Minneapolis 55455.
D R
DR
Knighton
G D
GD
Phillips
V D
VD
Fiegel
D000818:Animals; D003315:Cornea / Q000098:blood supply / Q000187:drug effects; D016039:Corneal Transplantation; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D005260:Female; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology / Q000502:physiology*; D020100:Hydrogels; D007700:Kinetics; D009389:Neovascularization, Pathologic; D011102:Polyhydroxyethyl Methacrylate / Q000031:analogs & derivatives / Q000494:pharmacology; D011145:Polyvinyls / Q000494:pharmacology; D011817:Rabbits; D014945:Wound Healing / Q000187:drug effects / Q000502:physiology*
D004343:Drug Implants; D020100:Hydrogels; D011145:Polyvinyls; C000257:polyhydroxyethyl methacrylate hydrogels; D016222:Fibroblast Growth Factor 2; C016438:ethylenevinylacetate copolymer; D011102:Polyhydroxyethyl Methacrylate