01373nas a2200193   4500000000100000000000100001008004100002260001500043653002300058653002700081100001500108700001800123700001900141245004500160856005500205300000900260520089600269022001401165       2023                            d  c2023-05-1110aMolecular medicine10atranslational research1 aAnna Loewa1 aJames J. Feng1 aSarah Hedtrich00aHuman disease models in drug development  uhttps://www.nature.com/articles/s44222-023-00063-3  a1-153 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