Engineering biomimetic intestinal topological features in 3D tissue models: retrospects and prospects

Conventional 2D intestinal models cannot precisely recapitulate biomimetic features in vitro and thus are unsuitable for various pharmacokinetic applications, development of disease models, and understanding the host-microbiome interactions. Thus, recently, efforts have been directed toward recreating in vitro models with intestine-associated unique 3D crypt-villus (for small intestine) or crypt-lumen (for large intestine) architectures. This review comprehensively delineates the current advancements in this research area in terms of the different microfabrication technologies (photolithography, laser ablation, and 3D bioprinting) employed and the physiological relevance of the obtained models in mimicking the features of native intestinal tissue. A major thrust of the manuscript is also on highlighting the dynamic interplay between intestinal cells (both the stem cells and differentiated ones) and different biophysical, biochemical, and mechanobiological cues along with interaction with other cell types and intestinal microbiome, providing goals for the future developments in this sphere. The article also manifests an outlook toward the application of induced pluripotent stem cells in the context of intestinal tissue models. On a concluding note, challenges and prospects for clinical translation of 3D patterned intestinal tissue models have been discussed.