Dose-finding study of fibrin gel-immobilized vascular endothelial growth factor 165 and basic fibroblast growth factor in the arteriovenous loop rat model

Tissue Eng Part A. 2009 Sep;15(9):2501-11. doi: 10.1089/ten.tea.2008.0477.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood Vessels / cytology
  • Blood Vessels / drug effects*
  • Dose-Response Relationship, Drug
  • Fibrin / pharmacology*
  • Fibroblast Growth Factor 2 / pharmacology*
  • Gels
  • Immobilized Proteins
  • Male
  • Models, Biological*
  • Rats
  • Rats, Inbred Lew
  • Tissue Scaffolds
  • Vascular Endothelial Growth Factor A / pharmacology*
  • X-Ray Microtomography

Substances

  • Gels
  • Immobilized Proteins
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • Fibroblast Growth Factor 2
  • Fibrin