Half‐Pipe Melt Electrowritten Scaffolds Support Engineering of an Immunocompetent Hydrogel‐Embedded Intestine‐on‐a‐Chip

In vitro models that mimic intestinal mucosal tissue inflammation and assess the sensitizing capacity of food proteins are essential for understanding food allergy mechanisms and improving safety assessments. Current 2D models lack spatial epithelial-immune cell interactions, including dendritic cell (DC) migration and DC-T cell crosstalk. Intestine-on-a-chip (IoC) models are used for infections and inflammatory bowel disease (IBD) but are not yet widely used in food allergy research. Here, a 3D immunocompetent IoC model is presented using extrusion-based bioprinting and melt electrowriting (MEW). The system integrates human intestinal epithelial cells (Caco-2) seeded on half-pipe-shaped MEW scaffolds and co-cultured with hydrogel-embedded monocyte-derived DCs (moDCs) inside the printed device. Subsequent moDC-T cell interactions are studied separately in a hydrogel-embedded system. IoCs exhibited leak-tight epithelial barriers comparable to transwell-like systems, while demonstrating higher metabolic and brush border enzyme activity, and lower LDH leakage. After food allergens (peanut, milk, and egg), non-allergen (Rubisco) or pro-inflammatory stimuli (toxin A and LPS) exposure, distinguishable effects on epithelial barrier integrity and moDC driven Th1/Th2 immune responses are observed. The IoC model presents a significant step toward 3D in vitro systems that mimic the intestinal mucosa's compartments to study food allergen sensitization and inflammatory diseases.