Animal testing has long been used in science to study complex biological phenomena that cannot be investigated using two-dimensional cell cultures in plastic dishes. With time, it appeared that more differences could exist between animal models and even more when translated to human patients. Innovative models became essential to develop more accurate knowledge. Tissue engineering provides some of those models, but it mostly relies on the use of prefabricated scaffolds on which cells are seeded. The self-assembly protocol has recently produced organ-specific human-derived three-dimensional models without the need for exogenous material. This strategy will help to achieve the 3R principles.