Human Umbilical Cord Mesenchymal Stem Cell‐Derived Extracellular Vesicles Loaded with Emodin Alleviate Intestinal Injury in Acute Pancreatitis

Acute pancreatitis (AP)‐induced intestinal barrier disruption drives fatal systemic complications. We engineered human umbilical cord mesenchymal stem cell‐derived extracellular vesicles (hUC‐MSC‐EVs) to deliver emodin—a bioactive compound limited by poor bioavailability—for targeted intestinal protection. In TNF‐α‐stimulated intestinal epithelial cells (CCD‐841CON), EV‐loaded emodin (EVs‐Emodin) synergistically suppressed NLRP3 inflammasome activation, pyroptosis, reactive oxygen species production, and inflammatory cytokines, outperforming monotherapies. EVs‐Emodin restored cell viability and curtailed apoptosis. In taurocholate‐induced AP mice, intravenous EVs‐Emodin attenuated systemic inflammation, promoted the expression of Occludin and ZO‐1, mitigated intestinal tissue lesions, promoted epithelial regeneration, inhibited inflammasome activation, and alleviated mitochondrial damage. hUC‐MSC‐EVs overcome emodin's delivery limitations, providing a synergistic strategy to protect the intestinal barrier via NLRP3/pyroptosis inhibition and oxidative stress mitigation, offering a promising therapeutic approach for AP‐associated intestinal injury.