Reductive alkylation of hyaluronic acid for the synthesis of biocompatible hydrogels by click chemistry

Carbohydr Polym. 2012 Nov 6;90(4):1704-11. doi: 10.1016/j.carbpol.2012.07.054. Epub 2012 Jul 28.

Abstract

Hyaluronan (HA) based hydrogels have been synthesized combining chemical modification of the polysaccharide by partial oxidation, reductive amination and 'click chemistry'. HA was oxidized by 4-acetamido-TEMPO-mediated reaction, using sodium hypochlorite as primary oxidant and NaBr in buffered pH, so that the produced aldehyde moieties (hemiacetals) were trapped in situ by adding primary amines containing azide or alkyne-terminal groups. The structure of the reaction products, oxidized-HA and primary amines bonded to HA, was elucidated using 2D NMR spectroscopy. SEC-MALLS analysis of the modified substrates showed a negligible degradation of the polysaccharide using this procedure. Furthermore, azido- and alkynyl derivatives underwent cross-linking by click chemistry into hydrogels, which were characterized by NMR, FT-IR, swelling degree and mechanical properties. Possible application of the material as scaffold for tissue engineering was tested by seeding and proliferation of chondrocytes for up to 15 days.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alkylation
  • Biocompatible Materials / chemical synthesis*
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Cells, Cultured
  • Chondrocytes / cytology
  • Chondrocytes / drug effects*
  • Chondrocytes / metabolism
  • Click Chemistry
  • Cross-Linking Reagents / chemistry*
  • Humans
  • Hyaluronic Acid / chemistry*
  • Hydrogels / chemical synthesis*
  • Rheology
  • Tissue Engineering

Substances

  • Biocompatible Materials
  • Cross-Linking Reagents
  • Hydrogels
  • Hyaluronic Acid