VEGF(165) and bFGF protein-based therapy in a slow release system to improve angiogenesis in a bioartificial dermal substitute in vitro and in vivo

• Published in: Langenbeck's archives of surgery Vol. 392; no. 3; pp. 305 - 314
• Main Authors: Wilcke, I, Lohmeyer, J A, Liu, S, Condurache, A, Krüger, S, Mailänder, P, Machens, H G
• Format: Journal Article
• Language: English
• Published: Germany 01.05.2007
• Subjects: Animals; Chondroitin Sulfates; Collagen; Delayed-Action Preparations - therapeutic use; Drug Delivery Systems; Endothelium, Vascular - cytology; Endothelium, Vascular - drug effects; Fibrin; Fibrin Tissue Adhesive; Fibroblast Growth Factor 2 - therapeutic use; Mice; Mice, Nude; Neovascularization, Physiologic - drug effects; Neovascularization, Physiologic - physiology; Recombinant Proteins - therapeutic use; Skin - blood supply; Time Factors; Vascular Endothelial Growth Factor A - therapeutic use; Wound Healing - drug effects
• ISSN: 1435-2443
• DOI: 10.1007/s00423-007-0194-1

Angiogenesis can be enhanced by several growth factors, like vascular endothelial growth factor-165 (VEGF(165)) and basic fibroblast growth factor (bFGF). Delayed release of such growth factors could be provided by incorporation of growth factors in fibrin matrices. In this study, we present a slow release system for VEGF(165) and bFGF in fibrin sealant. In vitro: Pieces of Integratrade mark matrix of 15 mm in diameter were prepared. Integratrade mark matrices were divided into four groups (A=control; B=fibrin sealant; C=fibrin sealant+growth factors; D=growth factors). In vivo: The bioartificial dermal templates were transplanted into a full-skin defect of the back of nu-nu mice. Four different groups included each six matrices at 2 and 4 weeks. In vitro: In groups C and D, continuous release of VEGF(165) and bFGF was eminent. The incorporation of growth factors into fibrin sealant evoked a prolonged growth factor release (p < 0.05). In vivo: A significantly higher amount of vessels was quantified in groups C and D compared to groups A and B (p < 0.001). A model of slow protein release by combining VEGF(165) and bFGF with fibrin sealant was produced. This model resulted in a prolonged bioavailability of growth factors in vivo for functional purposes. Fibrin and collagen can release growth factors in vivo and induce significant and faster neovascularisation in bioartificial dermal templates.