Insoluble hyaluronan films obtained by heterogeneous crosslinking with iron(III) as resorbable implants

We present water-insoluble hyaluronan films crosslinked by trivalent iron developed as potential resorbable implants. The films were crosslinked by sorption of ferric salt into solid HA films in water/2-propanol bath. These heterogeneously crosslinked films (het-FeHA) remained tough and dimensionally stable when rehydrated in saline. In contrast, films prepared by drying the well-known homogeneous ferric hyaluronate gels (hom-FeHA) softened upon rehydration and expanded rapidly. Differences between hom-FeHA and het-FeHA result from polymer network topology (dominant inter-or intra-molecular crosslink, respectively). Moreover, Mossbauer spectroscopy of het-FeHA revealed diiron complexes, while iron in the hom-FeHA was present exclusively as gamma-FeOOH nanoparticles or amorphous FeOOH. The biocompatibility tests of het-FeHA did not show any adverse effect and the sample disintegrated within one day when implanted in mice peritoneum. In conclusion, we developed implantable hyaluronan-based free-standing film with minimal swelling that can be resorbed quickly enough to avoid induction of foreign-body reaction.

Automated summary

Water-insoluble hyaluronan films crosslinked by trivalent iron were developed as potential resorbable implants by sorption of ferric salt into solid HA films. The heterogeneously crosslinked films remained tough and stable when rehydrated, leading to better biocompatibility compared to homogeneous ferric hyaluronate gels. Mossbauer spectroscopy revealed diiron complexes in the films, while the iron in homogeneous films existed as nanoparticles or amorphous structures.