Hybrid gels by conjugation of hyaluronic acid with poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro (5.5)undecane) copolymers.

The approach of covalent conjugation for coupling synthetic polymers with biomolecules represents an appealing strategy to produce new compounds with distinctive properties for biomedical applications. In the present study we generated hybrid gels with tunable characteristics by using hyaluronic acid (HA) and four variants of poly(itaconic anhydride-co-3,9-divinyl-2,4,8,10-tetraoxaspiro[5.5] undecane) (PITAU) copolymers, differing through the molar ratios between comonomers. The new bioconjugate compounds were realized by using a ″grafting to″ strategy, for further ensuring new ways for coupling of various bioactive compounds, taking into account that the grafted copolymers are dual sensitive to pH and temperature. The procedure of chemical crosslinking, by opening the anhydride cycle of the copolymer with the hydroxyl groups of hyaluronic acid, was used to prepare the bioconjugates. The chemical conjugation between HA and PITAU copolymers, as well as the structure of the new compounds, was confirmed by FTIR and NMR techniques. The physical properties of the new gels as thermal stability, swelling capacity, and rheological properties were investigated. The bioconjugate networks were also investigated as drug delivery carriers by using indomethacin as a model drug. In vitro and in vivo tests attested the homogeneity of the bioactive compounds as well as a good biochemical response, showing good biocompatibility for the new structures.