Enhancement of VEGF-Mediated Angiogenesis by 2-N,6-O-Sulfated Chitosan-Coated Hierarchical PLGA Scaffolds

ACS Appl Mater Interfaces. 2015 May 13;7(18):9982-90. doi: 10.1021/acsami.5b02324. Epub 2015 May 4.

Abstract

Rapid and controlled vascularization within scaffolds remains one of the key limitations in tissue engineering applications. This study describes the fabrication and characterization of 2-N,6-O-sulfated chitosan (26SCS)-coated hierarchical scaffold composed of poly(lactic-co-glycolic acid) (PLGA) microspheres, as a desirable vehicle for vascular endothelial growth factor (VEGF) delivery and consequent angiogenic boosting in vitro. Owing to the hierarchical porous structure and high affinity between VEGF and 26SCS, the 26SCS-modified PLGA (S-PLGA) scaffold possesses excellent entrapment and sustained release of VEGF. Using human umbilical vein endothelial cells (HUVECs) as a cell model, the VEGF-loaded S-PLGA scaffold shows desirable cell viability and attachment. The bioactivity of released VEGF is validated by intracellular nitric oxide secretion and capillary tube formation, demonstrating the improved capacity of VEGF-mediated pro-angiogenesis ascribed to 26SCS incorporation. Such a strategy will afford an effective method to prepare a scaffold with promoted angiogenesis.

Keywords: angiogenesis; poly(lactic-co-glycolic acid); scaffold; sulfated chitosan; vascular endothelial growth factor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Capillaries / drug effects
  • Capillaries / physiology
  • Cell Adhesion / drug effects
  • Cell Proliferation / drug effects
  • Cell Shape / drug effects
  • Cell Survival / drug effects
  • Chitosan / pharmacology*
  • Coated Materials, Biocompatible / pharmacology*
  • Human Umbilical Vein Endothelial Cells / cytology
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Intracellular Space / metabolism
  • Lactic Acid / pharmacology*
  • Microspheres
  • Neovascularization, Physiologic / drug effects*
  • Nitric Oxide / metabolism
  • Photoelectron Spectroscopy
  • Polyglycolic Acid / pharmacology*
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Porosity
  • Protein Binding / drug effects
  • Tissue Scaffolds / chemistry*
  • Vascular Endothelial Growth Factor A / pharmacology*

Substances

  • Coated Materials, Biocompatible
  • Vascular Endothelial Growth Factor A
  • chitosan sulfate
  • Polylactic Acid-Polyglycolic Acid Copolymer
  • Polyglycolic Acid
  • Nitric Oxide
  • Lactic Acid
  • Chitosan