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

J. Mrázek, J. Kohout, T. Kmječ, K. Nešporová, J. Chmelař, L. Kubala, V. Velebný

. 2021 ; 191 (-) : 201-210. [pub] 20210920

Language English Country Netherlands

Document type Journal Article

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, Mössbauer spectroscopy of het-FeHA revealed diiron complexes, while iron in the hom-FeHA was present exclusively as γ-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.

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$a We present water-insoluble hyaluronan films crosslinked by trivalent iron developed as potential resorbable implants. The films were crosslinked by sorption of ferric salt into solid HA films in water/2-propanol bath. These heterogeneously crosslinked films (het-FeHA) remained tough and dimensionally stable when rehydrated in saline. In contrast, films prepared by drying the well-known homogeneous ferric hyaluronate gels (hom-FeHA) softened upon rehydration and expanded rapidly. Differences between hom-FeHA and het-FeHA result from polymer network topology (dominant inter- or intra-molecular crosslink, respectively). Moreover, Mössbauer spectroscopy of het-FeHA revealed diiron complexes, while iron in the hom-FeHA was present exclusively as γ-FeOOH nanoparticles or amorphous FeOOH. The biocompatibility tests of het-FeHA did not show any adverse effect and the sample disintegrated within one day when implanted in mice peritoneum. In conclusion, we developed implantable hyaluronan-based free-standing film with minimal swelling that can be resorbed quickly enough to avoid induction of foreign-body reaction.
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$a Kohout, Jaroslav $u Faculty of Mathematics and Physics, Charles University, V Holešovičkách 2, 18000 Prague 8, Czechia
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$a Kmječ, Tomáš $u Faculty of Mathematics and Physics, Charles University, V Holešovičkách 2, 18000 Prague 8, Czechia
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$a Kubala, Lukáš $u Institute of Biophysics of the Czech Academy of Sciences, Královopolská 135, 612 65 Brno, Czechia; International Clinical Research Center, St. Anne's University Hospital, Pekařská 53, 656 91 Brno, Czechia
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