New physically and chemically crosslinked hyaluronate (HA)-based hydrogels for cartilage repair

When dissolved in aqueous solutions, sodium hyaluronate substituted with low amounts of alkyl chains [amphiphilic hyaluronate (HA)] can give rise to hydrogels thanks to intermolecular reversible hydrophobic interactions, leading to a three-dimensional (3D) network. Such hydrogels possess shear-thinning properties and can thus be injected in cartilage defect to promote chondrocyte proliferation and cartilage repair. However, these hydrogels are only physically crosslinked and can progressively loose their 3D structure when they are in contact with aqueous fluids. To overcome this drawback, HA derivatives substituted with dodecyl chains were chemically crosslinked by a difunctional reagent, tetraethylene glycol ditosylate (TEG-diOTs). To preserve the shear-thinning properties of amphiphilic HA, small amounts of TEG-diOTs were used so as to obtain a low chemical crosslinking ratio. After optimization of the synthesis parameters, aqueous solutions of the HA derivatives, crosslinked both physically and chemically, were obtained, with rheological properties improved compared to the amphiphilic polymers. As the hydrogels are aimed to cartilage repair, they were sterilized by wet heating; the effect of this treatment on the polymer characteristics was analyzed by different techniques. A similar study was carried out on HA derivatives stored under conditions mimicking physiological ones.