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.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Wilcke
I
I
Department of Plastic Surgery, Burn Unit, University Hospital of Schleswig-Holstein, Campus Lübeck, Lübeck, Germany. i.wilcke@web.de
Lohmeyer
J A
JA
Liu
S
S
Condurache
A
A
Krüger
S
S
Mailänder
P
P
Machens
H G
HG
D000818:Animals; D002809:Chondroitin Sulfates; D003094:Collagen; D003692:Delayed-Action Preparations / Q000627:therapeutic use; D016503:Drug Delivery Systems; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects; D005337:Fibrin; D015718:Fibrin Tissue Adhesive; D016222:Fibroblast Growth Factor 2 / Q000627:therapeutic use*; D051379:Mice; D008819:Mice, Nude; D018919:Neovascularization, Physiologic / Q000187:drug effects* / Q000502:physiology; D011994:Recombinant Proteins / Q000627:therapeutic use; D012867:Skin / Q000098:blood supply; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000627:therapeutic use*; D014945:Wound Healing / Q000187:drug effects
D003692:Delayed-Action Preparations; D015718:Fibrin Tissue Adhesive; D011994:Recombinant Proteins; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; C114835:integra artificial skin; D016222:Fibroblast Growth Factor 2; D005337:Fibrin; D002809:Chondroitin Sulfates; D003094:Collagen