Dual delivery of vascular endothelial growth factor and hepatocyte growth factor coacervate displays strong angiogenic effects.
Controlled delivery of multiple growth factors (GFs) holds great potential for the clinical treatment of ischemic diseases and might be more therapeutically effective to reestablish vasculature than the provision of a single GF. Vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF) are two potent angiogenic factors. However, due to rapid degradation and dilution in the body, their clinical potential will rely on an effective mode of delivery. A coacervate, composed of heparin and a biodegradable polycation, which protects GFs from proteolysis and potentiates their bioactivities, is developed. Here, the coacervate incorporates VEGF and HGF and sustains their release for at least three weeks. Their strong angiogenic effects on endothelial cell proliferation and tube formation in vitro are confirmed. Furthermore, it is demonstrated that coacervate-based delivery of these factors has stronger effects than free application of both factors and to coacervate delivery of each GF separately.
Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15261-3649, USA; McGowan Institute for Regenerative Medicine, Pittsburgh, Pennsylvania 15219-3110, USA.
Hassan K
HK
Awada
Noah R
NR
Johnson
Yadong
Y
Wang
D000704:Analysis of Variance; D002452:Cell Count; D016503:Drug Delivery Systems / Q000379:methods*; D042783:Endothelial Cells / Q000502:physiology; D005453:Fluorescence; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage / Q000494:pharmacology*; D061307:Human Umbilical Vein Endothelial Cells; D006801:Humans; D007511:Ischemia / Q000188:drug therapy*; D008855:Microscopy, Electron, Scanning; D008958:Models, Molecular; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D042461:Vascular Endothelial Growth Factor A / Q000008:administration & dosage / Q000494:pharmacology*
D042461:Vascular Endothelial Growth Factor A; D017228:Hepatocyte Growth Factor
angiogenesis; coacervate; drug delivery systems; growth factor; proteins