Immune-capable cervix-on-a-chip enables study of sexually transmitted infections

Sexually transmitted infections (STIs) not only impact an individual’s health, but also result in multibillion-dollar economic losses worldwide. To study these diseases, a team of researchers has developed the first-of-its-kind, immune-capable organ-on-a-chip model that realistically reproduces the human cervical environment, allowing scientists to study how the microbiome, immune system, and STIs interact—something that has not been possible before with oversimplified cell cultures or animal models.

Scientists from the University of Maryland School of Medicine (UMSOM) and School of Dentistry (UMSOD), the University of Delaware, and the University of Virginia have published the research in the journal Science Advances.

The heavy global toll of STIs

Chlamydia and gonorrhea represent a substantial share of the STI burden, with combined direct medical costs estimated at approximately $1 billion annually in the United States alone, driven by their high incidence and associated complications. Globally, the World Health Organization (WHO) reports nearly one million new STIs infections each day among people ages 15 to 49, including 129 million new chlamydia cases annually. Beyond their economic impact, chlamydia and gonorrhea can lead to serious complications in women’s health, including pelvic inflammatory disease, infertility, and adverse pregnancy outcomes such as preterm birth.

“This new model will revolutionize how scientists study STIs, leading to an improved understanding of these conditions, as well as the potential for better treatments,” said co-lead author Jacques Ravel, Ph.D., Director of the Center for Microbiome Research and Innovation (CAMRI) within UMSOM’s Institute for Genome Sciences (IGS); the John L. Whitehurst Professor of Medicine, Microbiology and Immunology, and Assistant Dean for Research Advancement at UMSOM.

“The other powerful part of this research has been its cross-discipline collaboration in the research. By integrating engineering, microbiology, immunology, and microbiome science, we were able to build a model that more closely reflects human biology and the complexity of the cervical microenvironment.”

How the cervical organ-on-a-chip works

The organ-on-a-chip model, scientifically known as a microphysiological system, simulates the human cervix using cervical epithelial cells, supportive tissue cells, immune cells, fluid flow, and microbiomes commonly found in the vagina. The model consists of a porous membrane layered with human cervical cells on one side and supportive cells on the other. Fluids flow across both sides, mimicking physiological conditions. When microbiomes and pathogens are added, the model replicates key aspects of what occurs in the human cervix.

“A key goal was to develop a complex model system that is both practical and accessible, enabling researchers outside of bioengineering labs to adopt it and apply it to answer important biological questions,” said co-lead author Jason Gleghorn, Ph.D., Associate Professor of Biomedical Engineering at the University of Delaware, who led the model development. “The need for this model was particularly critical for studying the vaginal microbiome, which we know plays an important role in susceptibility to STIs.”

Revealing the microbiome’s role in infection

After developing the model, the researcher team tested it using two sexually transmitted infections: chlamydia, caused by Chlamydia trachomatis; and gonorrhea, caused by Neisseria gonorrhoeae.

“One of the most exciting findings was that just like in women, protective microbiomes dominated by Lactobacillus crispatus limited infection in the model, highlighting further the critical role of the vaginal microbiome in STI risk. In contrast, when we introduced nonoptimal microbiomes, infections worsened,” said Dr. Ravel.

“This model provides a powerful new tool to develop faster, more effective, and personalized treatments, to test new therapies, such as probiotics or live biotherapeutics, to ultimately protect women from infections before they occur. For the first time, we can simulate what happens in the human body rather than relying solely on a petri dish systems or inadequate animal models.”