Synthetic biomimetic hydrogels incorporated with ephrin-A1 for therapeutic angiogenesis

Biomacromolecules. 2007 Jan;8(1):42-9. doi: 10.1021/bm060452p.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Biocompatible Materials / chemistry
  • Biomimetics
  • Cell Adhesion
  • Cells, Cultured
  • Dose-Response Relationship, Drug
  • Endothelium, Vascular / metabolism
  • Ephrin-A1 / chemistry*
  • Humans
  • Hydrogels / chemistry
  • Macromolecular Substances / chemistry
  • Models, Chemical
  • Neovascularization, Physiologic*
  • Photochemistry / methods
  • Tissue Engineering / methods


  • Biocompatible Materials
  • Ephrin-A1
  • Hydrogels
  • Macromolecular Substances