Toward endothelialization via vascular endothelial growth factor immobilization on cell-repelling functional polyurethanes

J Biomed Mater Res B Appl Biomater. 2019 May;107(4):965-977. doi: 10.1002/jbm.b.34190. Epub 2018 Sep 28.

Abstract

We screened a family of nonspecific cell-repelling polyurethanes (PUs) whose backbones are attached with epoxy group-terminated polyethylene glycol (PEG) side chains. Water incubation of the PU films (with 9.2-31.1 wt % PEG) caused a surface enrichment of PEG chains where vascular endothelial growth factor (VEGF) was grafted by forming secondary amine linkages between VEGF molecules and the PEG spacer. These linkages are still ionizable similar to original primary amines in VEGF, thereby retaining the original charge distribution on VEGF macromolecules. This charge conservation together with PEG steric repulsion helped to preserve VEGF conformation and bioactivity. The PU substrates with suitable hard segments contents and VEGF surface densities can selectively induce endothelial cells (ECs) adhesion and proliferation toward endothelialization. Moreover, the PU substrates, even grafted with fibrinogen (Fg), cannot trigger platelet adhesion and deformation, suggesting an inactive conformation of the grafted Fg. Thus enough antithrombogenicity of the PU substrates could be expected before full endothelialization. These PU materials might be applied onto the lumens of vascular grafts, potentially stimulating luminal endothelialization in vivo. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 107B: 965-977, 2019.

Keywords: endothelialization; polyethylene glycol; polyurethanes; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Coated Materials, Biocompatible* / chemistry
  • Coated Materials, Biocompatible* / pharmacology
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Immobilized Proteins* / chemistry
  • Immobilized Proteins* / pharmacology
  • Materials Testing*
  • Polyurethanes* / chemistry
  • Polyurethanes* / pharmacology
  • Vascular Endothelial Growth Factor A* / chemistry
  • Vascular Endothelial Growth Factor A* / pharmacology

Substances

  • Coated Materials, Biocompatible
  • Immobilized Proteins
  • Polyurethanes
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A