A millifluidic esophagus on-a-chip model for evaluating a natural remedy-mediated mucosal repair in GERD

Gastroesophageal reflux disease (GERD) is a common gastrointestinal disorder, characterized by the retrograde flow of gastric contents into the esophagus, causing symptoms such as heartburn and regurgitation. Although many patients with symptomatic GERD show no visible mucosal injury, impairment of its integrity at micro- scopic level is considered a relevant factor contributing to symptom generation and inflammation. In this sce- nario, protection of esophageal mucosa by topical agents has become a potential therapeutic approach. We investigated the protective and regenerative effects of a new natural formulation (GSE Reflusolve Rapid), using a dynamic culture based on MIVO® esophagus-on-chip platform, compared to an alginate/carbonate-based product. Results demonstrate that both products preserved esophageal integrity following acid stimulation, mitigating transepithelial electrical resistance (TEER) decline and upregulating MUC5B expression. Moreover, the natural formulation showed a significant reduction in IL-8 levels (p < 0.05) in contrast to the alginate-based formulation, despite the lack of a buffer action. TEER measurement, FITC-dextran permeability assay and his- tological analysis showed also the reparative properties of both mucosal protectants after acidic insult. In particular, the natural formulation showed a more pronounced and uniform expression of MUC5B throughout the tissue. These findings highlight that GSE Reflusolve Rapid may be a valid alternative to control long-term GERD- symptoms.