Reducing the inflammatory responses of biomaterials by surface modification with glycosaminoglycan multilayers

J Biomed Mater Res A. 2016 Feb;104(2):493-502. doi: 10.1002/jbm.a.35587. Epub 2015 Oct 29.

Abstract

Chronic inflammatory responses after implantation of biomaterials can lead to fibrotic encapsulation and failure of implants. The present study was designed to reduce the inflammatory responses to biomaterials by assembling polyelectrolyte multilayers (PEMs) composed of glycosaminoglycans (GAGs) and chitosan (Chi) on glass as model surfaces through layer-by-layer (LBL) technique. Surface plasmon resonance (SPR) and water contact angle (WCA) investigations confirmed the multilayer build-up with alternating deposition of GAGs and Chi layers, while zeta potential measurements showed significant negative charges after multilayer deposition, which further proved the PEM formation. Macrophage adhesion, macrophage spreading morphology, foreign body giant cell (FBGC) formation, as well as β1 integrin expression and interleukin-1β (IL-1β) production were all significantly decreased by GAG-Chi multilayer deposition in comparison to the primary poly (ethylene imine) (PEI) layer. Thereby, the type of GAGs played a pivotal role in inhibiting the inflammatory responses to various extents. Especially heparin (Hep)-Chi multilayers hindered all inflammatory responses to a significantly higher extent in comparison to hyaluronic acid (HA)-Chi and chondroitin sulfate (CS)-Chi multilayer systems. Overall, the present study suggests a great potential of GAG-Chi multilayer coating on implants, particularly the Hep-Chi based systems, to reduce the inflammatory responses.

Keywords: cytokines; glycosaminoglycans; inflammation; layer-by-layer technique; macrophages.

MeSH terms

  • Cell Line, Tumor
  • Chitosan / adverse effects
  • Chitosan / chemistry
  • Chitosan / pharmacology
  • Coated Materials, Biocompatible / adverse effects
  • Coated Materials, Biocompatible / chemistry
  • Coated Materials, Biocompatible / pharmacology*
  • Foreign-Body Reaction / metabolism
  • Foreign-Body Reaction / pathology
  • Foreign-Body Reaction / prevention & control*
  • Giant Cells, Foreign-Body / metabolism*
  • Giant Cells, Foreign-Body / pathology
  • Glycosaminoglycans / adverse effects
  • Glycosaminoglycans / chemistry
  • Glycosaminoglycans / pharmacology*
  • Humans
  • Inflammation / chemically induced
  • Inflammation / metabolism
  • Inflammation / pathology
  • Inflammation / prevention & control

Substances

  • Coated Materials, Biocompatible
  • Glycosaminoglycans
  • Chitosan