02135nas a2200409 4500000000100000000000100001008004100002260001500043653002700058653003500085653001800120653001800138653002300156100002000179700001800199700001400217700001900231700002100250700002100271700002100292700001800313700002000331700002000351700001500371700001300386700002000399700001900419700001700438700002400455700002100479245013100500856005500631300000900686490000700695520100900702022001401711 2024 d c2024-05-2910aBiomedical Engineering10aExperimental models of disease10aLab-on-a-chip10amicrofluidics10aTissue engineering1 aZohreh Izadifar1 aJustin Cotton1 aSiyu Chen1 aViktor Horvath1 aAnna Stejskalova1 aAakanksha Gulati1 aNina T. LoGrande1 aBogdan Budnik1 aSanjid Shahriar1 aErin R. Doherty1 aYixuan Xie1 aTania To1 aSarah E. Gilpin1 aAdama M. Sesay1 aGirija Goyal1 aCarlito B. Lebrilla1 aDonald E. Ingber00aMucus production, host-microbiome interactions, hormone sensitivity, and innate immune responses modeled in human cervix chips uhttps://www.nature.com/articles/s41467-024-48910-0 a45780 v153 aModulation of the cervix by steroid hormones and commensal microbiome play a central role in the health of the female reproductive tract. Here we describe organ-on-a-chip (Organ Chip) models that recreate the human cervical epithelial-stromal interface with a functional epithelial barrier and production of mucus with biochemical and hormone-responsive properties similar to living cervix. When Cervix Chips are populated with optimal healthy versus dysbiotic microbial communities (dominated by Lactobacillus crispatus and Gardnerella vaginalis, respectively), significant differences in tissue innate immune responses, barrier function, cell viability, proteome, and mucus composition are observed that are similar to those seen in vivo. Thus, human Cervix Organ Chips represent physiologically relevant in vitro models to study cervix physiology and host-microbiome interactions, and hence may be used as a preclinical testbed for development of therapeutic interventions to enhance women’s health. a2041-1723