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Studying sexually transmitted infections (STIs) has long been constrained by a fundamental problem: the available models fail to fully capture the complexity of the human body. Traditional cell cultures oversimplify biology, while animal models often do not accurately reflect human infection dynamics.

Now, scientists at the University of Maryland School of Medicine and collaborators have developed the first immune-capable “cervix-on-a-chip,” a microengineered system that recreates the human cervical environment with unprecedented realism. The work, published in Science Advances, could significantly accelerate the development of new treatments and prevention strategies for STIs.

A long-standing gap in STI research

STIs remain a major global health burden. According to the World Health Organization, nearly one million new infections occur every day worldwide, with chlamydia alone accounting for roughly 129 million cases annually. In the United States, chlamydia and gonorrhea together generate an estimated $1 billion in direct medical costs each year.

Beyond their prevalence, these infections can lead to serious complications, particularly in women, including infertility, pelvic inflammatory disease, and adverse pregnancy outcomes.

Despite this, researchers have struggled to study how infections develop and progress in the human cervix, a key site of infection, under realistic conditions.

“This new model will revolutionize how scientists study STIs,” said Jacques Ravel, PhD, co-lead author of the study. “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.”

Recreating the cervix in the lab

The newly developed system belongs to a class of technologies known as organ-on-a-chip models, or microphysiological systems. These platforms are designed to mimic the structure and function of human tissues using living cells and controlled physical environments.

In this case, the researchers constructed a miniature model of the cervix using human cervical epithelial cells layered on a porous membrane, with supportive tissue cells beneath. Fluids flow across both sides of the membrane, replicating the dynamic conditions found in the body.

The model also incorporates immune cells and microbial communities, allowing scientists to study how these components interact during infection.

“A key goal was to develop a complex model system that is both practical and accessible,” said Jason Gleghorn, PhD, 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.”

Capturing the role of the microbiome

One of the defining features of the cervix-on-a-chip is its ability to include different types of vaginal microbiomes, something that has been difficult to replicate in previous models.

The researchers tested the system using two of the most common STIs: chlamydia (Chlamydia trachomatis) and gonorrhea (Neisseria gonorrhoeae). They found that the outcome of infection depended strongly on the type of microbiome present.

In models dominated by Lactobacillus crispatus, a bacterial species commonly associated with vaginal health, infections were significantly limited. In contrast, when less protective microbiomes were introduced, infections became more severe.

“One of the most exciting findings was that just like in women, protective microbiomes dominated by Lactobacillus crispatus limited infection in the model,” Ravel said. “In contrast, when we introduced ‘nonoptimal’ microbiomes, infections worsened.”

These results reinforce growing evidence that the vaginal microbiome plays a central role in determining susceptibility to STIs.

Toward better treatments—and prevention

Beyond improving understanding, the new model provides a practical platform for testing potential therapies.

Because it closely mimics human biology, the cervix-on-a-chip can be used to evaluate new treatments under realistic conditions. This includes not only traditional antimicrobial drugs but also emerging approaches such as probiotics and live biotherapeutics designed to restore protective microbiomes.

“This model provides a powerful new tool to develop faster, more effective, and personalized treatments,” Ravel said. “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.”

A platform for broader applications

The implications of the technology extend beyond the infections tested in the study. The cervix-on-a-chip could be adapted to study a wide range of pathogens, as well as broader questions about reproductive health, inflammation, and host–microbe interactions.

The researchers emphasized accessibility in the model’s design, aiming to make it usable by scientists outside of specialized bioengineering labs. This could accelerate adoption and expand its impact across the field.

A step toward more human-relevant science

The development of immune-capable organ-on-a-chip systems represents a broader shift in biomedical research toward more human-relevant experimental models. By integrating multiple components of human biology—cells, tissues, immune responses, and microbiomes—these systems offer a more accurate view of disease processes.

In the context of STIs, where subtle interactions between host and microbes can determine outcomes, such realism is particularly valuable.

As researchers continue to refine these platforms, they may help bridge the gap between laboratory studies and real-world biology—ultimately enabling earlier, more precise, and more effective interventions.

For now, the cervix-on-a-chip marks a significant step forward, providing scientists with a tool that captures the complexity of the human cervix in a way that was previously out of reach.

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