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.

我们提出了由三价铁交联的水不溶性透明质酸薄膜，开发为潜在的可吸收植入物。通过在水/2-丙醇浴中将铁盐吸附成固体HA膜来使膜交联。当在盐水中再水化时，这些异质交联薄膜（het-FeHA）保持坚韧和尺寸稳定。相比之下，通过干燥众所周知的均质透明质酸铁凝胶 (hom-FeHA) 制备的薄膜在再水化时软化并迅速膨胀。hom-FeHA 和 het-FeHA 之间的差异源于聚合物网络拓扑结构（分别为主要的分子间或分子内交联）。此外，het-FeHA 的穆斯堡尔光谱揭示了二铁配合物，而 hom-FeHA 中的铁仅以 γ-FeOOH 纳米颗粒或无定形 FeOOH 的形式存在。het-FeHA 的生物相容性测试没有显示任何不利影响，当植入小鼠腹膜时，样品在一天内崩解。总之，我们开发了可植入的基于透明质酸的独立薄膜，其膨胀最小，可以足够快地再吸收，以避免诱发异物反应。