Synthetic biomimetic hydrogels incorporated with ephrin-A1 for therapeutic angiogenesis.
Eph receptors and ephrin ligands are essential for vascular development and angiogenic remodeling. In this work, we developed biomimetic poly(ethylene glycol)-diacrylate hydrogels incorporated with ephrin-A1 and examined their angiogenic properties. Ephrin-A1 was covalently immobilized on the surface of hydrogels by chemical modification and photopolymerization. Ephrin-A1 immobilized on hydrogels was found to retain its capacity to stimulate endothelial cell adhesion in a dose-dependent manner as similar findings were observed on polystyrene culture wells pre-adsorbed with ephrin-A1. Cell adhesion stimulated by ephrin-A1 was abolished by treatment with soluble RGDS and anti-alpha(v)beta3 integrin but not anti-alpha(v)beta5 integrin antibodies, suggesting that ephrin-A1 activates cell adhesion through alpha(v)beta3 integrins. Also, surface immobilized ephrin-A1 was found to induce endothelial tubule formation with luminal diameters ranging 5-30 microm on hydrogels. The results of these studies demonstrate that pro-angiogenic properties of ephrin-A1 are preserved in hydrogels and suggest potential applications of this hydrogel system in regenerative medicine and tissue engineering.
Moon
James J
JJ
Department of Bioengineering, Rice University, P.O. Box 1892, MS 142, Houston, Texas 77251-1892, USA.
Lee
Soo-Hong
SH
West
Jennifer L
JL
D001672:Biocompatible Materials / Q000737:chemistry; D032701:Biomimetics; D002448:Cell Adhesion; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000378:metabolism; D036382:Ephrin-A1 / Q000737:chemistry*; D006801:Humans; D020100:Hydrogels / Q000737:chemistry; D046911:Macromolecular Substances / Q000737:chemistry; D008956:Models, Chemical; D018919:Neovascularization, Physiologic; D010777:Photochemistry / Q000379:methods; D023822:Tissue Engineering / Q000379:methods
D001672:Biocompatible Materials; D036382:Ephrin-A1; D020100:Hydrogels; D046911:Macromolecular Substances