Injectable oxidized hyaluronic acid/adipic acid dihydrazide hydrogel for nucleus pulposus regeneration

Acta Biomater. 2010 Aug;6(8):3044-55. doi: 10.1016/j.actbio.2010.02.037. Epub 2010 Mar 1.


Injectable hydrogel allows irregular surgical defects to be completely filled, lessens the risk of implant migration, and minimizes surgical defects due to the solution-gel state transformation. Here, we first propose a method for preparing oxidized hyaluronic acid/adipic acid dihydrazide (oxi-HA/ADH) injectable hydrogel by chemical cross-linking under physiological conditions. Fourier transform infrared spectrometry and trinitrobenzene sulfonate assay were used to confirm the oxidation of hyaluronic acid. Rheological properties were measured to evaluate the working ability of the hydrogel for further clinical application. The oxi-HA/ADH in situ forming hydrogel can transform from liquid form into a gel-like matrix within 3-8 min, depending on the operational temperature. Furthermore, hydrogel degradation and cell assessment is also a concern for clinical application. Injectable oxi-HA/ADH8 hydrogel can maintain its gel-like state for at least 5 weeks with a degradation percentage of 40%. Importantly, oxi-HA/ADH8 hydrogel can assist in nucleus pulposus cell synthesis of type II collagen and aggrecan mRNA gene expression according to the results of real-time PCR analysis, and shows good biocompatibility based on cell viability and cytotoxicity assays. Based on the results of the current study, oxi-HA/ADH hydrogel may possess several advantages for future application in nucleus pulposus regeneration.

MeSH terms

  • Adipates / chemistry
  • Adipates / pharmacology*
  • Animals
  • Biocompatible Materials / pharmacology
  • Cell Survival / drug effects
  • Elastic Modulus / drug effects
  • Fluorescence
  • Gene Expression Regulation / drug effects
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / pharmacology*
  • Hydrogel, Polyethylene Glycol Dimethacrylate / pharmacology*
  • Injections
  • Intervertebral Disc / cytology*
  • Intervertebral Disc / drug effects
  • Intervertebral Disc / physiology*
  • Intervertebral Disc / ultrastructure
  • Materials Testing
  • Oxidation-Reduction / drug effects
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Rabbits
  • Regeneration / drug effects*
  • Rheology / drug effects
  • Spectroscopy, Fourier Transform Infrared
  • Staining and Labeling
  • Stress, Mechanical
  • Viscosity / drug effects


  • Adipates
  • Biocompatible Materials
  • RNA, Messenger
  • Hydrogel, Polyethylene Glycol Dimethacrylate
  • Hyaluronic Acid
  • adipic dihydrazide