Scientists designed ‘vagina on chip’ for research

Doctor Don Ingber makes organs for a living. Using flexible pieces of silicone etched with tiny channels, he grows tissues that can mimic the complex physical interactions between cells and fluids, creating three-dimensional, malleable models of organs.

Over the past decade, Ingber, a bioengineer at Harvard University, has made more than 15 of these organ chips, which simulate lungs, livers, intestines and skin. Now, as described in an article published last month, he has added a far less studied organ to the list: the vagina.

The “chip vagina” was made from vaginal cells donated by two women. The model was grown inside gum-sized pieces of silicone rubber, forming channels that responded to varying levels of estrogen and bacteria.

According to the study, the chip successfully mimicked key features of the vaginal microbiome — the communities of bacteria that play a crucial role in the health of the organ.

The chip is more realistic than other laboratory models of the organ: “It walks, it talks, it squawks [sic] like a human vagina,” Ingber said.

He and other researchers believe the tool could offer a better way to test treatments for bacterial vaginosis, an infection of harmful microbes that affects about 30% of women each year.

“This system is a major breakthrough,” said Dr. Ahinoam Lev-Sagie, a gynecologist at Hadassah Medical Center in Jerusalem who studies the vaginal microbiome and was not involved in the new study. Because of safety concerns, it’s difficult for researchers to test new treatments for patients with recurrent infections, she said.

It’s not hard to find women willing to donate vaginal samples, he explained. “But when you want to explore which drugs might work, it’s very difficult to find people willing to participate in the studies.”

The study, which was funded by the Bill and Melinda Gates Foundation, used the chip to mimic how a real vagina responds to both good and bad bacterial environments.

The researchers showed that the tissue inside the chip reacted positively to a cocktail of lactobacilli, a type of bacteria that digests sugars and produces lactic acid, creating an acidic environment inside the human vagina that protects it from infection.

When another type of bacteria that is associated with vaginal infections was grown on the chip without the presence of lactobacilli, inflammation increased and the cells were rapidly damaged.

This reaction is similar to what happens when a woman contracts bacterial vaginosis, a condition in which harmful bacteria take over the vaginal microbiome, decreasing its acidity and sometimes causing itching and increased discharge.

Bacterial vaginosis is usually treated with antibiotics, but relapse rates are high. When left untreated, bacterial vaginosis increases the risk of sexually transmitted infections and cervical cancer. In pregnant women, it may increase the risk of premature birth or low birth weight.

Despite these risks, bacterial vaginosis — and the vagina itself — remains understudied.

“We don’t really understand how these processes are triggered by bacteria in the vagina or even which bacteria are responsible,” said Amanda Lewis, a professor at the University of California San Diego who studies the vaginal microbiome. “As you can imagine, such a crude understanding of such an important physiological system results in either crude interventions or none at all.”

In 2019, Lev-Sagie and other researchers in Israel published the results of the world’s first vaginal microbiome transplants. They transferred bacteria-rich discharge from donors with healthy vaginas to five women suffering from recurrent bacterial vaginosis. Screening the samples to ensure they were safe and finding patients willing to participate was extremely difficult and took many years.

Other models, whether in animals or in the laboratory, are not effective environments for testing the vaginal microbiome. While healthy human vaginas are composed of about 70% lactobacilli, in other mammals lactobacilli rarely constitute more than 1% of the vaginal microbiome. And, when vaginal cells are mixed with bacteria in a flat petri dish, the bacteria quickly take over and kill the cells.

Similar disadvantages hamper the development of many drugs, which is why organ chips hold such promise, said Ingber, who holds the patent on the silicone chip and founded a company that manufactures and tests them.

“There has been a search for better in vitro models that really mimic the physiological complexity, the structural complexity of tissues,” he said. “That’s what we did with organ chips.”

In another paper published this week, Ingber’s group showed that a liver organ chip was seven to eight times better than animal models at predicting human reactions to 27 drugs.

But the “vagina chip” has limitations, the scientists said.

Lev-Sagie of Hadassah Medical Center in Jerusalem has observed that the vaginal microbiome changes substantially in response to menstruation, intercourse, hormone fluctuations and antibiotic use. And other important types of cells in the vagina, such as immune cells, were not included in the study.

“Real life is much more complex than the vagina on chip,” said Lev-Sagie.

Having a more sophisticated model will require more studies into exactly how the vaginal microbiome works and how it responds to disease, she added.

Unlike gut microbiome research, which has progressed rapidly over the last decade, work on the vaginal microbiome suffers from a lack of funding.

“We’ve known for over a hundred years that the bacteria in the vagina are crucial,” said Lev-Sagie. “We’ve been researching for many years, but we’re still behind.”

_{Translated by Luiz Roberto M. Gonçalves}