A Nanosheet-Anchored Hydrogel System: An Injectable Platform for Herbs Polyphenols in Treating Ulcerative Colitis

Natural polyphenols derived from medicinal herbs exhibit significant anti-inflammatory and tissue-repair properties, demonstrating considerable therapeutic potential for inflammatory injury diseases such as ulcerative colitis (UC). However, the development of sustained-release carriers compatible with polyphenols remains a critical challenge. In this study, we engineered a hydrogel system by integrating Cayratia japonica polyphenols with boric acid-modified manganese dioxide nanosheets (MNS) into a hyaluronic acid–dopamine (HA–DA) matrix for targeted UC therapy. The designed hydrogel exhibited a three-dimensional porous architecture and mucoadhesive characteristics, facilitating the sustained release of therapeutic components in the colonic microenvironment. In vitro studies demonstrated synergistic therapeutic effects, including oxygen generation, reactive oxygen species (ROS) scavenging, and controlled polyphenols release. In vivo assessments using murine colitis models revealed that the hydrogel significantly mitigated disease progression, as evidenced by attenuated body weight loss, reduced disease activity index (DAI) scores, and suppression of colon shortening. Histopathological and immunofluorescence analyses further confirmed the restoration of the intestinal epithelial barrier through upregulation of tight junction proteins (Claudin-1 and ZO-1) and modulation of macrophage polarization (M1-to-M2 phenotype transition). This multifunctional hydrogel platform represents a promising strategy for the in situ delivery of natural polyphenols, offering a potent and targeted approach for UC intervention.