Scientists Create Immune-Capable ‘Cervix-on-a-Chip’ to Study Sexually Transmitted Infections

Sexually transmitted infections (STIs) not only impact health but also can lead to multibillion-dollar economic losses worldwide. To stem these physiological and financial losses, researchers have developed a first-of-its-kind immune-capable “organ-on-a-chip” model that realistically reproduces the human cervical environment, thus allowing scientists to study ways in which the microbiome, immune system, and STIs interact—an experience that has been impossible 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 published the research in the journal Science Advances.

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, driven by their high incidence and associated complications. Globally, the World Health Organization (WHO) reports nearly 1 million new STIs infections daily 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-disciplinary 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.”

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,” stated 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.”

After developing the model, the research 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,” Dr. Ravel commented. “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 petri dish systems or inadequate animal models.”

The Institute for Genome Sciences’ (IGS) has been part of the University of Maryland School of Medicine (UMSOM) since 2007. IGS scientists work in diverse areas, applying genomics and systems biology approaches to better understand health issues and create a healthier world. Its research spans multiple areas including cancer and precision medicine; parasitic, fungal, and bacterial diseases; sexual and reproductive health; the underpinnings of aging; and neuroscience areas including brain development, addiction, and mental health. IGS also remains at the forefront of high-throughput genomic technologies and bioinformatics analyses through its core facility, Maryland Genomics, which provides researchers worldwide with cutting-edge, collaborative, and cost-effective sequencing and analysis. 

The University of Delaware College of Engineering partners with industry, government, and academia to advance solutions that drive economic growth, strengthen national priorities, and improve quality of life. Its faculty leads more than $130 million in annual research spanning areas such as advanced manufacturing, clean energy, artificial intelligence, and biomedical innovation. Through hands-on education and interdisciplinary collaboration, the college prepares more than 3,500 students to become leaders in engineering and computing.