A Scalable Microarrayed Organoid Platform for Precision Modeling of Intestinal Epithelial Damage and Recovery

Existing preclinical in vitro models of IBD have limitations in accurately reproducing the dynamic processes of epithelial barrier dysfunction and repair, which hinders the translation of research findings into new therapeutic approaches.

Here, we established a scalable, microarrayed 3D human intestinal organoid platform that enables high-throughput, single-organoid resolution modeling of inflammation-induced epithelial damage and subsequent regenerative responses, recapitulating both morphological and transcriptional signatures of biopsy-derived mucosal tissues from Crohn’s disease patients. Employing time-resolved morphological imaging, transcriptomics, and a novel quantitative epithelial recovery metric, introduced as the 'Intestinal Organoid Recovery Score (IORS),' we distinguished responder organoids to preventive and therapeutic bioactives, notably dexamethasone (DEX), nicotinamide (NAM), and β-hydroxybutyrate (BHB).