title: Sustained (rh)VEGF(165) release from a sprayed fibrin biomatrix induces angiogenesis, up-regulation of endogenous VEGF-R2, and reduces ischemic flap necrosis.
abstract: This study investigated (1) the release of recombinant human vascular endothelial growth factor ([rh]VEGF(165)) from an in vitro fibrin matrix, (2) the effects of (rh)VEGF(165) released from an in vivo fibrin matrix on ischemic flap necrosis in the rat dorsal skin flap model, and (3) the effects of (rh)VEGF(165) released from an in vivo fibrin matrix on VEGF-R2 expression in transgenic VEGF-R2/luc mice. In vitro fibrin matrices were spiked with (rh)VEGF(165) and demonstrated (rh)VEGF(165) release over 88 hours with 66% recovery. Ischemic dorsal flaps were treated with a fibrin sealant (FS), FS spiked with (rh)VEGF(165), or left untreated. Flaps treated with FS spiked with (rh)VEGF(165) showed greater viability than controls as measured by planimetric analysis. Immunohistochemical analyses revealed stronger neovascularization than that exhibited by controls. Transgenic mice implanted with FS spiked with (rh)VEGF(165) had significant increases in VEGF-R2 expression relative to controls at days 5-13 after implantation. Conclusions drawn from this work are that (1) (rh)VEGF(165) is released from an in vitro fibrin matrix at clinically appropriate times, (2) (rh)VEGF(165) increases the viability of tissue flaps in vivo, and (3) (rh)VEGF(165) induces the expression of VEGF-R2 expression. This work demonstrates the clinical ability of sprayed FS to locally deliver growth factors to ischemic tissue of patients.
authors.affiliation: Ludwig Boltzmann Institute for Experimental and Clinical Traumatology, Vienna, Austria. Rainer.Mittermayr@lbitrauma.org
authors.forename: Rainer
authors.initials: R
authors.lastname: Mittermayr
authors.forename: Tatjana
authors.initials: T
authors.lastname: Morton
authors.forename: Martina
authors.initials: M
authors.lastname: Hofmann
authors.forename: Sam
authors.initials: S
authors.lastname: Helgerson
authors.forename: Martijn
authors.initials: M
authors.lastname: van Griensven
authors.forename: Heinz
authors.initials: H
authors.lastname: Redl
mesh_terms: D000818:Animals; D016009:Chi-Square Distribution; D004797:Enzyme-Linked Immunosorbent Assay; D015718:Fibrin Tissue Adhesive / Q000008:administration & dosage / Q000494:pharmacology*; D007124:Immunoenzyme Techniques; D007511:Ischemia / Q000517:prevention & control*; D051379:Mice; D008822:Mice, Transgenic; D009336:Necrosis / Q000517:prevention & control; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018709:Statistics, Nonparametric; D013524:Surgical Flaps / Q000098:blood supply*; D013718:Tensile Strength; D015854:Up-Regulation; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology*; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism
chemical_list: D015718:Fibrin Tissue Adhesive; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D040301:Vascular Endothelial Growth Factor Receptor-2