title: Evaluation of blood vessel ingrowth in fibrin gel subject to type and concentration of growth factors.
abstract: Our aim was to quantitatively assess the angiogenetic effects of VEGF and bFGF immobilized in a fibrin-based drug delivery system in a suitable subcutaneous rat model. After evaluation of a suitable implantation technique (6 rats), four teflon isolation chambers containing fibrin gel matrices were implanted subcutaneously in an upside-down fashion on the back of 30 Lewis rats. The matrices consisted of 500 microl fibrin gel with two different fibrinogen concentrations (10 mg/ml or 40 mg/ml fibrinogen) and 2 I.U./ml thrombin and contained VEGF and bFGF in five different concentrations (0 to 250 ng/ml each). At 3, 7 and 14 days after implantation, matrices were explanted and subjected to histological and morphometrical analysis. At 1 week, the volume of the fibrin clots was significantly smaller in the 100 and 250 ng/ml VEGF and bFGF groups in comparison to lower concentrated growth factors. At 1 and 2 weeks, the use of growth factors in low concentrations (25 ng/ml VEGF and bFGF) significantly increased the amount of fibrovascular tissue, average fraction of blood vessels and number of blood vessels at the matrix-host interface in comparison to growth factor-free controls. Higher concentrations were neither associated with further increase of tissue formation nor with increased sprouting of blood vessels in this model. This study demonstrates that fibrin gel-immobilized angioinductive growth factors efficiently stimulate generation of fibrovascular tissue and sprouting of blood vessels in a newly developed subcutaneous upside-down isolation chamber model with an optimum between 25 and 100 ng/ml.
authors.affiliation: Department of Plastic and Hand Surgery, University of Erlangen Medical Center, Erlangen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Arkudas
authors.forename: J
authors.initials: J
authors.lastname: Tjiawi
authors.forename: A
authors.initials: A
authors.lastname: Saumweber
authors.forename: J P
authors.initials: JP
authors.lastname: Beier
authors.forename: E
authors.initials: E
authors.lastname: Polykandriotis
authors.forename: O
authors.initials: O
authors.lastname: Bleiziffer
authors.forename: R E
authors.initials: RE
authors.lastname: Horch
authors.forename: U
authors.initials: U
authors.lastname: Kneser
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects* / Q000254:growth & development*; D005337:Fibrin / Q000494:pharmacology*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D005782:Gels; D008297:Male; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D019919:Prosthesis Implantation; D051381:Rats; D011917:Rats, Inbred Lew; D013194:Staining and Labeling; D042442:Vascular Endothelial Growth Factors / Q000494:pharmacology*
chemical_list: D005782:Gels; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D005337:Fibrin