On the demixing of hyaluronan and alginate in the gel state

The manuscript focuses on the demixing of hyaluronan and alginate in the hydrogel state. Binary solutions of the two polysaccharides have been treated with Ca²⁺ as the alginate cross-linking ion and the radial distribution of the two components in the hydrogels was measured by means of ¹H NMR. These results revealed the presence of alginate-enriched and hyaluronan-enriched domains stemming from a polysaccharide demixing. The hydrogels were characterized by means of uniaxial compression and creep-compliance measurements which showed that the demixing increased the overall resistance of the hydrogel to stress. In addition, due to the viscoelastic properties of hyaluronan, a marked increase of the Newtonian viscosity of the constructs was noticed. The peculiarity of the effect of hyaluronan was demonstrated by the use of an alginate unable to form gel by binding non-calcium binding alginate, i.e. mannuronan, ruling out the effect of viscosity over the time-dependent behavior of the mixed hyaluronan-alginate hydrogels.