Stiffness of polyelectrolyte multilayer film influences endothelial function of endothelial cell monolayer

Colloids Surf B Biointerfaces. 2017 Jan 1:149:379-387. doi: 10.1016/j.colsurfb.2016.11.012. Epub 2016 Nov 9.

Abstract

Endothelialization has proved to be critical for maintaining long-term success of implantable vascular devices. The formation of monolayer of endothelial cells (ECs) on the implant surfaces is one of the most important factors for the endothelialization. However, endothelial function of regenerated EC monolayer, which plays a much more important role in preventing the complications of post-implantation, has not received enough attention. Here, a vascular endothelial growth factor (VEGF)-incorporated poly(l-lysine)/hyaluronan (PLL/HA) polyelectrolyte multilayer film was fabricated. Through varying the crosslinking degree, stiffness of the film was manipulated, offering either soft or stiff film. We demonstrated that ECs were able to adhere and proliferate on both soft and stiff films, subsequently forming an integrated EC monolayer. Furthermore, endothelial functions were evaluated by characterizing EC monolayer integrity, expression of genes correlated with the endothelial functions, and nitric oxide production. It demonstrated that EC monolayer on the soft film displayed higher endothelial function compared to that on the stiff film. Our study highlights the influence of substrate stiffness on endothelial function, which offers a new criterion for surface design of vascular implants.

Keywords: Endothelial cell; Endothelial function; Polyelectrolyte multilayer films; Substrate stiffness; Vascular endothelial growth factor.

MeSH terms

  • Antigens, CD / genetics
  • Antigens, CD / metabolism
  • Biglycan / genetics
  • Biglycan / metabolism
  • Cadherins / genetics
  • Cadherins / metabolism
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Collagen Type IV / genetics
  • Collagen Type IV / metabolism
  • Elastic Modulus
  • Fibronectins / genetics
  • Fibronectins / metabolism
  • Gene Expression Regulation / drug effects
  • Hardness
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects*
  • Human Umbilical Vein Endothelial Cells / metabolism
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Membranes, Artificial
  • Nitric Oxide / biosynthesis
  • Nitric Oxide Synthase Type III / genetics
  • Nitric Oxide Synthase Type III / metabolism
  • Platelet Endothelial Cell Adhesion Molecule-1 / genetics
  • Platelet Endothelial Cell Adhesion Molecule-1 / metabolism
  • Polyelectrolytes / chemistry
  • Polyelectrolytes / pharmacology*
  • Polylysine / chemistry
  • Polylysine / pharmacology*
  • Surface Properties
  • Vascular Endothelial Growth Factor A / metabolism
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Antigens, CD
  • Biglycan
  • Cadherins
  • Collagen Type IV
  • Fibronectins
  • Membranes, Artificial
  • Platelet Endothelial Cell Adhesion Molecule-1
  • Polyelectrolytes
  • VEGFA protein, human
  • Vascular Endothelial Growth Factor A
  • cadherin 5
  • Polylysine
  • Nitric Oxide
  • Hyaluronic Acid
  • NOS3 protein, human
  • Nitric Oxide Synthase Type III