Assessing the toxicity of chemical substances to human health requires reliable experimental models that accurately reflect human physiology. The intestine represents a major interface between the human body and its environment, yet current cellular models fail to fully reproduce its structural organization and physical properties. This PhD project aims to develop advanced intestinal models using three-dimensional biomimetic materials (BAM). Through 3D printing technologies, these materials will reproduce key architectural features of the intestine, including its crypts and villi. An innovative, patented coating, whose mechanical properties can be tuned independently of scaffold geometry, will mimic essential characteristics of the intestinal extracellular matrix. Intestinal organoid-derived cells will be cultured on these scaffolds to develop models that more closely resemble human intestinal physiology. The project will investigate how microenvironmental geometry and stiffness influence intestinal cell organization, differentiation, and function. The resulting models will then be exposed to reference chemicals with known toxicological effects. Cellular responses will be analyzed and compared with those obtained using conventional culture models. The objective is to determine whether better reproducing the intestinal microenvironment can improve the sensitivity, reproducibility, and physiological relevance of toxicity testing. This interdisciplinary project will combine biomaterials engineering, cell biology, mechanobiology, and toxicology. Ultimately, these advanced intestinal models could also contribute to reducing the reliance on animal experimentation.