Specific VEGF sequestering and release using peptide-functionalized hydrogel microspheres

Biomaterials. 2012 Apr;33(12):3475-84. doi: 10.1016/j.biomaterials.2012.01.032. Epub 2012 Feb 7.

Abstract

Growth factor signaling plays an essential role in regulating processes such as tissue development, maintenance, and repair. Gene expression levels, diffusion, degradation, and sequestration by extracellular matrix components all play a role in regulating the concentration of growth factors within the cellular microenvironment. Herein, we describe the synthesis and characterization of hydrogel microspheres that mimic the ability of the native extracellular matrix to reversibly bind vascular endothelial growth factor (VEGF) out of solution. A peptide ligand derived from the VEGF receptor 2 (VEGFR2) was covalently incorporated into the hydrogel microspheres in order to achieve binding affinity and specificity. In addition to being able to both bind and release VEGF in a controllable manner, the microspheres were also shown to affect human umbilical vein endothelial cell (HUVEC) proliferation. The resulting microspheres may enable new strategies to specifically upregulate or downregulate growth factor signaling in the cellular microenvironment.

Publication types

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

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cattle
  • Cell Proliferation
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemical synthesis
  • Hydrogel, Polyethylene Glycol Dimethacrylate / chemistry*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / metabolism*
  • Microspheres*
  • Molecular Sequence Data
  • Peptides / chemical synthesis
  • Peptides / chemistry*
  • Peptides / metabolism*
  • Protein Binding
  • Serum / metabolism
  • Vascular Endothelial Growth Factor A / chemistry
  • Vascular Endothelial Growth Factor A / metabolism*

Substances

  • Peptides
  • Vascular Endothelial Growth Factor A
  • Hydrogel, Polyethylene Glycol Dimethacrylate