01596nas a2200325   4500000000100000000000100001008004100002260001200043653001200055653002700067653001100094653000900105653001300114653001600127653002000143653001400163653002500177653001300202653002200215100002300237700001900260700001900279700001700298700001700315245008500332300001400417490000700431520081800438022001401256       2022                            d  c2022-1110aAnimals10aDisease Models, Animal10aFemale10aMale10aRodentia10aSex Factors10aorgan-on-a-chip10aorganoids10aPreclinical research10asex bias10asexual dimorphism1 aSonya Kouthouridis1 aEleanor Robson1 aAlicia Hartung1 aSandeep Raha1 aBoyang Zhang00aSe(XY) matters: the importance of incorporating sex in microphysiological models  a1284-12980 v403 aThe development of microphysiological models is currently at the forefront of preclinical research. Although these 3D tissue models are being developed to mimic physiological organ function and diseases, which are often sexually dimorphic, sex is usually neglected as a biological variable. For decades, national research agencies have required government-funded clinical trials to include both male and female participants as a means of eliminating male bias. However, this is not the case in preclinical trials, which have been shown to favor male rodents in animal studies and male cell types in in vitro studies. In this Opinion, we highlight the importance of considering sex as a biological variable and outline five approaches for incorporating sex-specific features into current microphysiological models.  a1879-3096