01391nas a2200205   4500000000100000000000100001008004100002260001200043653002300055653002700078100001500105700001800120700001900138245004500157856005500202300001200257490000600269520089600275022001401171       2023                            d  c2023-0810aMolecular medicine10atranslational research1 aAnna Loewa1 aJames J. Feng1 aSarah Hedtrich00aHuman disease models in drug development  uhttps://www.nature.com/articles/s44222-023-00063-3  a545-5590 v13 aBiomedical research is undergoing a paradigm shift towards approaches centred on human disease models owing to the notoriously high failure rates of the current drug development process. Major drivers for this transition are the limitations of animal models, which, despite remaining the gold standard in basic and preclinical research, suffer from interspecies differences and poor prediction of human physiological and pathological conditions. To bridge this translational gap, bioengineered human disease models with high clinical mimicry are being developed. In this Review, we discuss preclinical and clinical studies that benefited from these models, focusing on organoids, bioengineered tissue models and organs-on-chips. Furthermore, we provide a high-level design framework to facilitate clinical translation and accelerate drug development using bioengineered human disease models.  a2731-6092