Sustained (rh)VEGF₁₆₅ 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.

Extracorporeal Shock Wave Therapy (ESWT) Minimizes Ischemic Tissue Necrosis Irrespective of Application Time and Promotes Tissue Revascularization by Stimulating Angiogenesis

“…These results are comparable with other studies using exogenous growth factors (eg, therapeutic angiogenesis) to limit ischemic tissue necrosis. 1,2 There are a number of clinically relevant attributes of therapeutic low energy shock waves that are distinctly more advantageous than pharmacotherapeutic angiogenesis. Shock wave therapy is a safe, easy-to-use, noninvasive, low-cost modality, devoid of any drug interactions.…”

Hypoxia inducible microRNA 210 attenuates keratinocyte proliferation and impairs closure in a murine model of ischemic wounds

“…The need for experimental models of ischemic wounds is therefore compelling. Skin flaps represent a proven classical approach to induce ischemia (5,6,(21)(22)(23). In this study, the flap dimensions were optimized such that the tissue was ischemic but not necrotic.…”

Characterization of a preclinical model of chronic ischemic wound

“…Using the re-epithelialized area as the numerator and the original width as the denominator and multiplying by 100 gives the percentage of the wound re-epithelialized (E/W) ϫ 100 ϭ percent re-epithelialization. Data are means Ϯ SD (n ϭ 3); *P Ͻ 0.05. classical approach to induce ischemia (14,27,28,37,60). In this study, the flap dimensions were optimized such that the tissue was ischemic but not necrotic.…”