Thermosensitive chitosan-gelatin-glycerol phosphate hydrogel as a controlled release system of ferulic acid for nucleus pulposus regeneration

Biomaterials. 2011 Oct;32(29):6953-61. doi: 10.1016/j.biomaterials.2011.03.065. Epub 2011 Jul 19.

Abstract

In the degenerative disc, overproduction of reactive oxygen species (ROS) involves in apoptosis and senescence of nucleus pulposus (NP) cells that could accelerate the degenerative process. Ferulic acid (FA) has been reported to have an excellent antioxidant property. In the study, injectable thermosensitive chitosan/gelatin/glycerol phosphate (C/G/GP) hydrogel was applied as a controlled release system for FA delivery. The study was aimed to evaluate possible therapeutic effects of FA-incorporated C/G/GP hydrogel on hydrogen peroxide (H(2)O(2))-induced oxidative stress NP cells. The results showed that the release of FA from C/G/GP hydrogel could decrease the H(2)O(2)-induced oxidative stress. Post-treatment of FA-incorporated C/G/GP hydrogel on H(2)O(2)-induced oxidative stress NP cells showed up-regulation of Aggrecan and type II collagen and down-regulation of MMP-3 in mRNA level. The results of sulfated-glycosaminoglycans (GAGs) to DNA ratio and alcian blue staining revealed that the GAGs production of H(2)O(2)-induced oxidative stress NP cells could reach to normal level. The results of caspase-3 activity and TUNEL staining indicated that FA-incorporated C/G/GP hydrogel decreased the apoptosis of H(2)O(2)-induced oxidative stress NP cells. The results suggested that the C/G/GP hydrogel was very suitable for sustained delivery of FA. The FA-incorporated C/G/GP hydrogel would be used to treat the degenerative disc in the early stage before it developed into the latter irreversible stages.

Publication types

  • Evaluation Study

MeSH terms

  • Animals
  • Caspase 3 / metabolism
  • Chitosan / chemistry*
  • Coumaric Acids / chemistry
  • Coumaric Acids / metabolism
  • Coumaric Acids / pharmacology*
  • Delayed-Action Preparations / chemistry*
  • Drug Carriers / chemistry
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / metabolism
  • Free Radical Scavengers / pharmacology
  • Gelatin / chemistry*
  • Gene Expression / drug effects
  • Glycerol / chemistry*
  • Glycosaminoglycans / chemistry
  • Glycosaminoglycans / metabolism
  • Hydrogels / chemistry*
  • Hydrogen Peroxide / pharmacology
  • In Situ Nick-End Labeling
  • Intervertebral Disc / cytology
  • Intervertebral Disc / drug effects*
  • Intervertebral Disc / pathology
  • Intervertebral Disc / physiology
  • Materials Testing
  • Oxidants / pharmacology
  • Oxidative Stress / drug effects
  • Rabbits
  • Reactive Oxygen Species / metabolism
  • Regeneration / drug effects*
  • Temperature
  • Tissue Engineering / methods

Substances

  • Coumaric Acids
  • Delayed-Action Preparations
  • Drug Carriers
  • Free Radical Scavengers
  • Glycosaminoglycans
  • Hydrogels
  • Oxidants
  • Reactive Oxygen Species
  • Gelatin
  • Chitosan
  • ferulic acid
  • Hydrogen Peroxide
  • Caspase 3
  • Glycerol