An Advanced Cervix-on-a-Chip Enables Mechanistic Studies of the Host-Microbiome-Pathogen Interactions
A new Ravel lab study published in Science Advances reports the development of a novel microphysiologicalsystem that recreates the human cervical environment and enables researchers to study, in unprecedented detail, how the microbiome, immune system, and sexually transmitted pathogens interact. The work represents a close collaboration between the Ravel lab at the Center for Advanced Microbiome Research and Innovation (CAMRI), the University of Delaware, and the University of Virginia, bringing together complementary expertise in bioengineering, microbiology, immunology, and microbiome science.
The project’s team comprised Dr. Jason Gleghorn, a bioengineer at the University of Delaware, Drs. Isabelle Derré and Alison Criss, both microbiologists at the University of Virginia, Dr. Patrik Bavoil at the University of Maryland School of Dentistry, and Dr. Jacques Ravel’s laboratory. Together, the team developed a modular, accessible “organ-on-a-chip” platform that models the structure and function of human cervical tissue, including epithelial cells, fibroblasts, immune components, and microbial communities. Unlike traditional cell culture, this system captures key features of the cervicovaginal environment, including fluid flow, microbial colonization, and immune cell recruitment, enabling the study of infections in a physiologically relevant context.
“This project is a powerful example of what can be achieved through true interdisciplinary collaboration,” said Jacques Ravel, PhD. “By integrating engineering, microbiology, and microbiome science, we were able to build a model that much more closely reflects human biology and the complexity of the cervical microenvironment.”
A central innovation of the study is not only the platform's design but also its successful implementation across multiple independent laboratories, demonstrating that it is both reproducible and transferable. “A key goal from the beginning was to create a system that could be used beyond a bioengineering lab,” said Jason Gleghorn, PhD. “We designed this platform to be accessible and practical, so that researchers without specialized engineering expertise can adopt it and apply it to important biological questions.” This need is particularly acute in the study of the vaginal microbiome, which is fundamentally distinct in humans from that of other animals. Unlike humans, animals do not typically harbor Lactobacillus-dominated communities or maintain the acidic vaginal pH that characterizes a healthy human cervicovaginal environment, limiting the physiological relevance of existing in vivo and in vitro models for studying microbiome–host interactions in infectious diseases.
Using this system, the researchers showed that it supports infection by two major sexually transmitted pathogens, Chlamydia trachomatis and Neisseria gonorrhoeae, and reproduces essential aspects of the host response, including immune cell recruitment. The model also revealed how strongly the vaginal microbiome shapes infection outcomes. Communities dominated by Lactobacillus crispatus, which are associated with health, significantly reduced chlamydial infection and limited its propagation, while non-optimal microbiota promoted inflammation and increased susceptibility to infection.
“Our ability to incorporate defined microbial communities into this system allows us to directly test how the microbiome influences susceptibility to infection,” said Vonetta Edwards, PhD, a Research Associate at CAMRI. “This is something that has been very difficult to achieve with existing models.” Alison Criss, PhD, added, “The platform also enables us to capture immune responses in a controlled and human-relevant setting, which is critical for understanding disease mechanisms.”
By providing a system that integrates host tissue, microbiota, and immune components, this work represents an important step forward for studying infections of the female reproductive tract. The platform is low-cost and does not require specialized infrastructure, making it broadly accessible and well-positioned to accelerate discovery across laboratories.
“This is not just a new model, it is a new way to study host-microbiome-pathogen interactions,” Jacques Ravel, PhD, said. “It opens the door to identifying mechanisms and testing interventions, including live biotherapeutics, in ways that were not previously possible.”
As interest in microbiome-based therapies continues to grow, tools like this cervical microphysiological system will be essential for translating fundamental discoveries into new strategies to prevent and treat infections, ultimately improving women’s health worldwide.
April 15, 2026