Synthesis of highly substituted amide hyaluronan derivatives with tailored degree of substitution and their crosslinking via click chemistry

Hyaluronan (HA) based hydrogels with well defined 3D-molecular architecture have been synthesized combining chemical modification of hyaluronic acid and 'click chemistry'. The high degree of substitution of HA was obtained after activation of the carboxyl group with ethyl chloroformate and subsequent functionalization of the carboxylic group with primary amine containing either a terminal azido or alkynyl groups. The degree of amide substitution could be controlled by reaction conditions. The chemical modification probed to be highly chemo-selective providing only amide modified HA derivates. The prepared derivates showed higher resistance towards thermal degradation than starting hyaluronan material. The crosslinking reaction of azido- and alkynyl-amide derivates of HA led to the formation of highly organized and porous networks, which due to their high stability against degradation are potential candidates for application as drug delivery systems, or scaffolds in tissue engineering. (C) 2011 Elsevier Ltd. All rights reserved.