Alleviation of tissue adhesion using dual-functional methacrylated gelatin via immunomodulation and antifibrotic activity

Intestinal adhesion is one of the most prevalent clinical conditions, affecting millions of patients globally. However, effective strategies to decrease the incidence of intestinal adhesion remain insufficient. In this study, we developed a novel and unreported dual-functional methacrylated gelatin (nhGelMA) that can regulate inflammation and antifibrotic functions by integrating gelatin methacryloyl (GelMA), Houttuynia cordata extract, and nintedanib. First, optimal concentrations of GelMA hydrogels were prepared and screened, followed by the selection of appropriate concentrations of Houttuynia cordata extract and nintedanib to prepare the final nhGelMA. Subsequently, nhGelMA was characterized, and its biocompatibility and biological functions were analyzed. The results indicated that nhGelMA exhibited good biocompatibility, no organ toxicity, and the ability to modulate the expression level of inflammation and fibronectin (FN). Finally, nhGelMA hydrogel was applied in the preventive treatment of hemorrhagic intestinal adhesion, and the results indicated that nhGelMA effectively reduced the deposition of FN, laminin (LAMA), and collagen type I (Col1), as well as decreased the infiltration of macrophages and neutrophils, thereby preventing the occurrence of intestinal adhesion. Importantly, the further transcriptomics demonstrated that nhGelMA could regulate protein digestion, absorption, and adhesion, as well as reconstruct the anatomical structure, contributing to the alleviation of hemorrhagic intestinal adhesion.