3D-Printed Functional Engineered Intestinal Models

Abstract

The intestine is a vital organ, orchestrating nutrient absorption, immune surveillance, and barrier integrity functions essential for human physiological homeostasis. Traditional in vitro intestinal models, such as 2D monolayers and static organoids, lack the complex architecture, multi-layer cellular organization, and dynamic physicochemical microenvironment of native tissue, leading to poor predictive power for drug response and disease mechanisms. The rapid evolution of 3D bioprinting, however, is changing this landscape. It has become a central focus in preclinical research to construct biomimetic intestinal models that faithfully replicate native tissue architecture, cellular diversity, and microenvironmental cues. This review systematically summarizes the latest research progress in 3D-printed biomimetic intestinal models. We delve into bioprinting techniques, bioink formulation, cell sources, structural fabrication strategies, and the quest for functional biomimicry. We also explore their integration with organ-on-a-chip systems and their expanding applications in drug screening, intestinal development, diseases and tissue repair. Central to our discussion is how technological leaps, like novel bioinks and innovative printing methods, are enabling the reconstruction of complex gut architectures. Despite remarkable progress, hurdles remain in achieving full physiological maturity, scalability, standardization, and cost-effectiveness. Finally, we discuss future research directions aimed at enhancing model fidelity, enabling multi-organ integration, and strengthening their translational potential.