One-pot synthesis of α,β-unsaturated polyaldehyde of chondroitin sulfate

• Published in: Carbohydrate polymers 2016-01, Vol.136, p.1002-1009
• Main Authors: Bobula, Tomáš, Buffa, Radovan, Procházková, Pavlína, Vágnerová, Hana, Moravcová, Veronika, Šuláková, Romana, Židek, Ondřej, Velebný, Vladimír
• Format: Article
• Language: English
• Subjects: 3T3 Cells; Aldehydes - chemistry; Animals; Biocompatible Materials - adverse effects; Biocompatible Materials - chemical synthesis; Biocompatible Materials - chemistry; Cell Survival; Chondroitin sulfate; Chondroitin Sulfates - chemistry; Cross-Linking Reagents - chemistry; Crosslinking; Fibroblasts - drug effects; Hydrogel; Mice; Oxidation; Tissue engineering
• ISSN: 0144-8617; 1879-1344
• DOI: 10.1016/j.carbpol.2015.10.005

•Chemoselective modification of CS under mild reaction conditions was developed.•A new derivative of CS – α,β-unsaturated polyaldehyde was synthetized in one pot.•pH-responsive conjugation of α,β-unsaturated aldehyde with various amines was demonstrated.•The crosslinking of α,β-unsaturated aldehyde was performed under physiological conditions and led to well organized and porous structures – hydrogel scaffolds.•α,β-Unsaturated aldehyde of CS is a promising and biocompatible material for drug delivery and tissue engineering. Chondroitin sulfate (CS) was chemoselectively oxidized by Tempo/NaClO to C-6 aldehyde of a d-galactosamine subunit (GalNAc). The subsequent, spontaneous desulfatation of oxidized CS gave rise to α,β-unsaturated aldehyde. A new derivative of CS was fully characterized and a degree of oxidation was determined by spectroscopic analysis. The optimization of reaction conditions showed a proportional degree of oxidation to an amount of sodium hypochlorite. The utility of α,β-unsaturated aldehyde for crosslinking and conjugation was demonstrated by a seamless condensation with various N-nucleophiles. We also demonstrated pH-dependent release of biologically active agents from oxidized CS. A live-dead assay in the presence of α,β-unsaturated aldehyde revealed unaffected viability of NIH 3T3 fibroblasts, which made this precursor promising for several biomedical applications including drug delivery and tissue engineering.