title: Reductive alkylation of hyaluronic acid for the synthesis of biocompatible hydrogels by click chemistry.
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.
authors.affiliation: Contipro Biotech, Dolni Dobrouč 401, 561 02 Dolni Dobrouč, Czech Republic. huerta-angeles@contipro.com
authors.forename: Gloria
authors.initials: G
authors.lastname: Huerta-Angeles
authors.forename: Miroslava
authors.initials: M
authors.lastname: Němcová
authors.forename: Eva
authors.initials: E
authors.lastname: Příkopová
authors.forename: Daniela
authors.initials: D
authors.lastname: Šmejkalová
authors.forename: Martin
authors.initials: M
authors.lastname: Pravda
authors.forename: Lukáš
authors.initials: L
authors.lastname: Kučera
authors.forename: Vladimír
authors.initials: V
authors.lastname: Velebný
mesh_terms: D000478:Alkylation; D001672:Biocompatible Materials / Q000138:chemical synthesis*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D057930:Click Chemistry; D003432:Cross-Linking Reagents / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000737:chemistry*; D020100:Hydrogels / Q000138:chemical synthesis*; D012212:Rheology; D023822:Tissue Engineering
chemical_list: D001672:Biocompatible Materials; D003432:Cross-Linking Reagents; D020100:Hydrogels; D006820:Hyaluronic Acid