The effect of aminooxy-linkers’ structure on the mechanical properties of hyaluronan-oxime hydrogels

Abstract

The wide range of hydrogel applications is a result of the optimization of gelation. Herein, the various aminooxylinkers were synthesized to study the kinetics of gelation and mechanical properties of hydrogels prepared by crosslinking of aldehyde-modified N-acetylglucosamine (GlcNAc) of hyaluronan (ΔHA-CHO: 4,5-anhydro-6-(GlcNAc)-oxo hyaluronan or HA-CHO: 6-(GlcNAc)-oxo hyaluronan). Structural characteristics of the linkers (length, number of functional groups and rigidity) and the polymer (effect of the –C=C- double bond) were investigated in detail and showed decreasing mechanical stiffness with increasing hydrophobic character of linker and effect of its rigidity/flexibility on imine conversion. Besides known linear bis(aminooxy)alkanes with different lengths of the chain, new multifunctional aminooxy-linkers: 1,3,5-tris(aminooxymethyl)benzene and multikis(6-aminooxy-6-deoxy)-β-cyclodextrin were prepared and shortened the gelation time. The MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) analysis showed that despite the aminooxylinkers ´ cytotoxicity at higher concentrations, the final oxime hydrogels are non-cytotoxic and therefore are suitable for medicinal applications.

Keywords

• polymer gels
• hyaluronan
• rheology
• oxyamine