The intestinal epithelium is the fastest self-renewing organ in mammals, continuously adapting to environmental changes. This is due to the action of resident intestinal stem cells (ISCs). A concerted effort has been taken over the last years to generate ex vivo culture systems sustaining the long-term maintenance of primary intestinal epithelium. The landmark identification of the LGR5 receptor as a bona-fide ISC marker led to the establishment of murine intestinal organoids. Almost immediately, “mini-guts” started to be derived from different human tissue sources, including colorectal cancer in the form of tumoroids to better recapitulate disease. These milestones are being progressively fused with microfabrication to create engineered systems that more closely replicate organ-specific design in a gut-on-chip format. Despite extraordinary advancements, standardization and reproducibility issues associated with the need to achieve higher physiological complexity still limit the preclinical value of these models.

In this collection, we invite the submission of articles exploring architectural, biochemical, mechanical and/or microenvironmental features in the context of intestinal tissue 3D modelling. The main goal is to bring together innovative techniques as well as improved procedures focused on (but not limited to) generating stem cell-derived intestinal tissue biomimics, manipulating gene regulatory networks in these culture systems, and examining cell renewal and differentiation as functional readouts of the established models. The proposed methodologies will add to the arsenal of tools available to boost our understanding of basic gut homeostasis and pathology and might ultimately shorten the path for the clinical translation of intestinal tissue surrogates.