title: Dose-finding study of fibrin gel-immobilized vascular endothelial growth factor 165 and basic fibroblast growth factor in the arteriovenous loop rat model.
abstract: The angiogenic effects of different concentrations of vascular endothelial growth factor (VEGF) 165 and basic fibroblast growth factor (bFGF) immobilized in a fibrin-based drug-delivery system were quantitatively assessed in the arteriovenous (AV) loop model. An AV loop was created in the medial thigh of 60 rats. The loop was placed in a Teflon isolation chamber and embedded in 500 microL of fibrin gel loaded with VEGF and bFGF in four different concentrations (no growth factor, 100 ng/mL of VEGF, 25 ng/mL of VEGF and bFGF, 100 ng/mL pf VEGF and bFGF). The explantation intervals were 1, 2, and 4 weeks after the initial operation for all groups. Specimens were investigated using (micro-CT) and histological and morphometrical techniques. After 2 weeks, the cross-section area and construct weight were significantly lower with the use of 100 ng/mL of VEGF and bFGF. Micro-CT and histology showed significantly greater vascular density and number of vessels of the constructs at 2 and 4 weeks when 100 ng/mL of VEGF165 and bFGF were applied than in the growth factor-free specimens. The angioinductive effects were dose-dependent, with best results when using 100 ng/mL of VEGF165 and bFGF. The greater tissue formation was accompanied by faster resorption of the fibrin matrix.
authors.affiliation: Department of Plastic and Hand Surgery, University of Erlangen Medical Center, Erlangen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Arkudas
authors.forename: Galyna
authors.initials: G
authors.lastname: Pryymachuk
authors.forename: Tobias
authors.initials: T
authors.lastname: Hoereth
authors.forename: Justus P
authors.initials: JP
authors.lastname: Beier
authors.forename: Elias
authors.initials: E
authors.lastname: Polykandriotis
authors.forename: Oliver
authors.initials: O
authors.lastname: Bleiziffer
authors.forename: Raymund E
authors.initials: RE
authors.lastname: Horch
authors.forename: Ulrich
authors.initials: U
authors.lastname: Kneser
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000166:cytology / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D005337:Fibrin / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005782:Gels; D055767:Immobilized Proteins; D008297:Male; D008954:Models, Biological; D051381:Rats; D011917:Rats, Inbred Lew; D054457:Tissue Scaffolds; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*; D055114:X-Ray Microtomography
chemical_list: D005782:Gels; D055767:Immobilized Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; D005337:Fibrin