Stimulation of Microvascular Networks on Sulfonated Polyrotaxane Surfaces with Immobilized Vascular Endothelial Growth Factor

Macromol Biosci. 2019 Apr;19(4):e1800346. doi: 10.1002/mabi.201800346. Epub 2019 Jan 9.

Abstract

Modulation of material properties and growth factor application are critical in constructing suitable cell culture environments to induce desired cellular functions. Sulfonated polyrotaxane (PRX) surfaces with immobilized vascular endothelial growth factors (VEGFs) are prepared to improve network formation in vascular endothelial cells. Sulfonated PRXs, whereby sulfonated α-cyclodextrins (α-CDs) are threaded onto a linear poly(ethylene glycol) chain capped with bulky groups at both terminals, are coated onto surfaces. The molecular mobility of sulfonated PRX surfaces is modulated by tuning the number of threading α-CDs. VEGF is immobilized onto surfaces with varying mobility. Low mobility and VEGF-immobilization reinforce cell proliferation, yes-associated protein activity, and rhoA, pdgf, ang-1, and pecam-1 gene expression. Highly mobile surfaces and soluble VEGF weakly affect these cell responses. Network formation is strongly stimulated in vascular endothelial cells only on low-mobility VEGF-immobilized surfaces, suggesting that molecular mobility and VEGF immobilization synergistically control cell function.

Keywords: human umbilical vein endothelial cell; molecular mobility; polyrotaxane; surface-immobilization of growth factor; vascular endothelial growth factor; vascular network.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biocompatible Materials / chemistry*
  • Cyclodextrins / chemistry*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / metabolism*
  • Humans
  • Immobilized Proteins* / chemistry
  • Immobilized Proteins* / pharmacology
  • Microvessels / growth & development*
  • Poloxamer / chemistry*
  • Polyethylene Glycols / chemistry
  • Rotaxanes / chemistry*
  • Surface Properties
  • Vascular Endothelial Growth Factor A* / chemistry
  • Vascular Endothelial Growth Factor A* / pharmacology
  • alpha-Cyclodextrins / chemistry

Substances

  • Biocompatible Materials
  • Cyclodextrins
  • Immobilized Proteins
  • Rotaxanes
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • alpha-Cyclodextrins
  • polyrotaxane
  • Poloxamer
  • Polyethylene Glycols