Bacterial vaginosis (BV), affecting over 25% of reproductive-aged women, represents a significant unmet need in women’s health. This condition, caused by pathogenic bacteria disrupting the healthy microbiomes in the female vagina and cervix, triggers inflammation leading to severe discomfort and complications such as increased risks of HIV, other sexually transmitted diseases, spontaneous abortion, pre-term birth, and pelvic inflammatory diseases.
Traditionally, antibiotics have been the sole treatment for BV, yet they often fail to eradicate the bacteria and prevent recurrence in over 60% of cases. Despite being identified over a century ago, the pathogenic events following BV infection remain poorly understood, hindering the development of more effective treatments.
Addressing this gap, researchers at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the University of California Davis, led by Wyss Founding Director Donald Ingber, M.D., Ph.D., have developed a microfluidic human cervix-on-a-chip (Cervix Chip). This model replicates the complex interactions of cervical epithelial cells, the protective mucus layer they produce, and the cervical microbiome, both in healthy states and when attacked by BV-causing bacteria.
The study, published in *Nature Communications*, describes how the team created an organ chip model of the cervical wall. By growing human cervical epithelial cells and cervical fibroblast cells in parallel channels of a microfluidic device, separated by a porous membrane, they were able to replicate the interactions and region-specific mechanical cues found in a woman’s body.
The Cervix Chip also successfully mimicked the cervix’s mucus production and its changes under the influence of sex hormones and microbial communities. This innovative model offers new insights into cervix functionality and vulnerability, setting a new standard in research.
Researchers found that exposing the Cervix Chip to periodic fluid flow generated a thin monolayered epithelium typical of the endocervix, while continuous fluid flow produced a thick ectocervix-like multi-layered epithelium. The chip also responded to sex hormone levels by altering the mucus’s thickness, water content, and sugar structures, reflecting natural cervix physiology.
In studying BV, the researchers observed that the presence of healthy Lactobacillus crispatus bacteria improved mucus quality and maintained epithelial integrity. In contrast, the presence of pathogenic Gardnerella vaginalis bacteria compromised the epithelium’s barrier functions and elevated inflammation-related protein expression.
This cervix-on-a-chip model, developed in collaboration with the University of California Davis and the National Museum of the Republic of Kazakhstan, holds promise for finding new treatments for BV and other infectious diseases of the female reproductive tract. The technology enables researchers to evaluate potential treatments’ efficacy and gain comprehensive insights into the cervix’s tissue and microbial components’ relevance in various pathologies.
