PEG-cross-linked heparin is an affinity hydrogel for sustained release of vascular endothelial growth factor.
An affinity-based controlled release system for growth factors having heparin-binding domains was prepared using a cross-linked heparin gel. The heparin gel was made by reacting hydrazide-functionalized heparin (Hep-ADH) with the N-hydroxysuccinimidyl ester of poly(ethylene glycol)-bis-butanoic acid (SBA-PEG-SBA). The degree of cross-linking could be controlled by defining the stoichiometry of hydrazide modification and the PEG cross-linker addition. The release of vascular endothelial growth factor (VEGF) was characterized as a heparin-binding growth factor. VEGF was directly injected into the heparin gel and the loaded VEGF displayed a slow, controlled release over 3 weeks with little initial burst phase. The biological activity of the released VEGF was measured with a proliferation assay utilizing human umbilical vein endothelial cells. The released VEGF maintained its biological activity at all time points investigated. The heparin gel with loaded VEGF was implanted sub-cutaneously in the dorsal region of mice. A significantly increased density of the endothelial cell marker platelet endothelial adhesion molecule (PECAM-1) was observed in histological specimens of the tissues surrounding the implanted gel.
Tae
Giyoong
G
Department of Bioengineering, University of Washington, Seattle 98195, USA.
Scatena
Marta
M
Stayton
Patrick S
PS
Hoffman
Allan S
AS
D000818:Animals; D003432:Cross-Linking Reagents / Q000737:chemistry*; D003692:Delayed-Action Preparations; D006493:Heparin / Q000737:chemistry*; D020100:Hydrogels / Q000737:chemistry* / Q000633:toxicity; D020407:Internet; D007700:Kinetics; D051379:Mice; D015394:Molecular Structure; D018919:Neovascularization, Physiologic / Q000187:drug effects; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000378:metabolism; D011092:Polyethylene Glycols / Q000737:chemistry*; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000494:pharmacology*
D003432:Cross-Linking Reagents; D003692:Delayed-Action Preparations; D020100:Hydrogels; D019408:Platelet Endothelial Cell Adhesion Molecule-1; D042461:Vascular Endothelial Growth Factor A; D011092:Polyethylene Glycols; D006493:Heparin