A silicone chip lined with tissue from human donors could help scientists test drug treatments for bacterial infections in the vagina.
Dr. Don Ingber makes organs for a living. Using flexible pieces of silicone carved with tiny channels, he grows tissues that can mimic the complex physical interactions between cells and fluids, creating malleable, three-dimensional models of organs.
Over the past decade, Dr. Ingber, a bioengineer at Harvard, has made more than 15 of these organ chips, including those simulating lungs, livers, intestines and skin. And now, as described in a paper published last month, he has added a far less studied organ to the list: the vagina.
The “vagina on a chip” was made from vaginal cells donated by two women. The model was grown inside of silicone rubber chips the size of a stick of gum, forming channels that were responsive to fluctuating estrogen levels and bacteria. The chip successfully mimicked key features of the vaginal microbiome, the swarming communities of bacteria that play a crucial role in the organ’s health, the study found.
The chip is more realistic than other laboratory models of the organ, Dr. Ingber said: “This walks, talks, quacks like a human vagina.”
He and other researchers are optimistic that the tool could offer a better way to test treatments for bacterial vaginosis, an infection of harmful microbes in the vagina which affects an estimated 30 percent of women every year.
“This is a great development, this system,” 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 is difficult for researchers like her to test new treatments for patients with recurring infections, she said.
It’s not difficult to find women willing to donate vaginal samples, she said. “But when you want to explore which medications can work, it’s very, very difficult to find women who are willing to participate in these studies.”
The study, which was funded by the Gates Foundation, used the vagina chip to mimic how a real vagina responds to good and bad bacterial environments. The researchers showed that the tissue inside the chip reacted positively to a cocktail of Lactobacilli, a type of bacterium that digests sugars and produces lactic acid, creating an acidic environment inside the human vagina that protects it from infections. When a different type of bacterium, one associated with vaginal infections, was cultured on the chip with no Lactobacilli present, inflammation increased and the cells were quickly damaged.
That reaction is similar to what happens when someone contracts bacterial vaginosis, a condition in which harmful bacteria take over the vaginal microbiome, lowering its acidity and sometimes causing itching and increased discharge.
Bacterial vaginosis is typically 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 can raise the risk of preterm 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 often even which bacteria are responsible,” said Amanda Lewis, a professor at the University of California, San Diego, who studies the vaginal microbiome. “As you might imagine, such a crude understanding of such an important physiological system makes for crude interventions or none at all.”
In 2019, Dr. 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 into the vaginas of five women who had struggled with recurring bacterial vaginosis. Screening the samples to make sure that they were safe and finding patients that were willing to participate was extremely difficult and took many years.
Other models, in animals or in the lab, are not effective environments in which to test the vaginal microbiome. While the vaginas of healthy humans are made up of around 70 percent Lactobacilli, in other mammals Lactobacilli rarely constitute more than 1 percent of the vaginal microbiome. And when vaginal cells are mixed with bacteria in a flat petri dish, bacteria quickly take over and kill the cells.
Similar drawbacks hamper the development of many drugs, which is why the organ chips are so promising, said Dr. Ingber, who holds a patent for the design of the silicone chip and founded a company that makes and tests them.
“There’s been a search for better in vitro models that really mimic the physiological complexity, the structural complexity of tissues,” he said. “And so that’s what we’ve done with organ chips.”
In another paper published this week, Dr. Ingber’s group showed that an organ chip of the liver was seven to eight times better at predicting human responses to 27 drugs than animal models.
But the vagina chip has limitations, scientists said.
Dr. Lev-Sagie of Hadassah Medical Center in Jerusalem noted that the vaginal microbiome shifts substantially in response to menstruation, sexual intercourse, hormonal 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 complicated than the vagina on a chip,” Dr. Lev-Sagie said.
Having a more sophisticated model will require more studies of how exactly the vaginal microbiome works and how it responds to disease, she added. Unlike research on the gut microbiome, which has progressed rapidly over the past decade, work on the vaginal microbiome suffers from a lack of funding.
“In the vagina, we knew that bacteria are crucial more than a hundred years ago,” Dr. Lev-Sagie said. “We do the research for many years, but we still lag behind.”