Sustained (rh)VEGF165release from a sprayed fibrin biomatrix induces angiogenesis, up‐regulation of endogenous VEGF‐R2, and reduces ischemic flap necrosis

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Abstract
This study investigated (1) the release of recombinant human vascular endothelial growth factor ([rh]VEGF165) from an in vitro fibrin matrix, (2) the effects of (rh)VEGF165released from an in vivo fibrin matrix on ischemic flap necrosis in the rat dorsal skin flap model, and (3) the effects of (rh)VEGF165released from an in vivo fibrin matrix on VEGF‐R2 expression in transgenic VEGF‐R2/luc mice. In vitro fibrin matrices were spiked with (rh)VEGF165and demonstrated (rh)VEGF165release over 88 hours with 66% recovery. Ischemic dorsal flaps were treated with a fibrin sealant (FS), FS spiked with (rh)VEGF165, or left untreated. Flaps treated with FS spiked with (rh)VEGF165showed 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)VEGF165had significant increases in VEGF‐R2 expression relative to controls at days 5–13 after implantation. Conclusions drawn from this work are that (1) (rh)VEGF165is released from an in vitro fibrin matrix at clinically appropriate times, (2) (rh)VEGF165increases the viability of tissue flaps in vivo, and (3) (rh)VEGF165induces 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.

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