We investigated the angiogenic bioactivity and therapeutic angiogenic effect of vascular endothelial growth factor (VEGF) administration by the heparin-functionalized nanoparticle-fibrin gel complex. The markedly increased bioactivity was observed by the VEGF-loaded nanoparticle-fibrin gel complex, compared to the VEGF-loaded fibrin gel, the nanoparticle-fibrin gel complex without VEGF, or fibrin gel (control) in terms of the capillary density in a mouse subcutaneous implantation model. Furthermore, the VEGF-loaded nanoparticle-fibrin gel complex significantly enhanced the therapeutic angiogenic effect in a rabbit ischemic hind limb model: the noticeable increase in the recovered calf blood pressure, the angiographic score, and the density of collaterals, as well as the stable maintenance of the organized collaterals, compared to the VEGF-loaded fibrin gel. These results show the enhanced angiogenic potential of VEGF administration by the proposed heparin-functionalized nanoparticle-fibrin gel complex.
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