3D-Printed Ovaries in Mice Could One Day Help Infertile Women Become Pregnant

The first 3D-printed soft tissue organ that has been successful in an animal model holds the promise of eventual human reproductive trials in the future.

Women who undergo chemotherapy and other harsh drug treatments suffer from a range of side effects, including diminished fertility. These drugs can damage a woman’s ovaries, making it difficult, or impossible, for her to conceive. But scientists have now engineered a new way of restoring fertility using three ingredients: gelatin, a 3D printer, and mice.

Three litters of healthy mouse pups have been birthed from bioprosthetic ovaries, scientists announced this week, renewing hope for fertility treatments in women who have undergone treatment for cancer. The ovaries, created with 3D printers, might one day be scaled up to function in women whose reproductive systems have been diminished due to chemotherapy or other harsh medical treatments.

“This research shows these bioprosthetic ovaries have long-term, durable function,” said Teresa K. Woodruff, a reproductive scientist and member of the research team, in a press statement. “Using bioengineering, instead of transplanting from a cadaver, to create organ structures that function and restore the health of that tissue for that person, is the holy grail of bioengineering for regenerative medicine.”

The study, published in Nature Communications, explained how scientists used gelatin to create the “scaffolding” of functional ovaries tiny enough to be implanted in live mice. The synthetic ovaries, which already contained follicles — small sacks that contain immature ovum, or eggs — allowed the mice to mate naturally, give birth, and secrete hormones for lactation just as they would with natural ovaries.

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This is the first 3D-printed soft tissue organ that has been successful in an animal model, said Monica Laronda, co-lead author of the study and a former post-doctoral fellow in the Woodruff Lab at Northwestern University.

The key, Laronda told Seeker, lies in two places: the gelatin used to make the ovaries, and the geometry of the scaffolding. Though it is safe to use in humans, gelatin is a tricky material to work with because it easily collapses. In previous trials, the printed gelatin became either too spread out or too clumpy. But this time, the researchers found a printing temperature where the gelatin not only remained stable, but also strong and self-supporting.

“People have printed with gelatin before,” said Laronda, “just not in this beautifully homogenous, self-supporting way.”

She and her colleagues used a 3D printer to create thin parallel ribbons of gelatin that were then offset at 60 degrees. The result “kind of looks like a stretched-out diamond,” Laronda remarked. These shapes were then stacked in groups of five to create a structure that is a mere two millimeters across.

The structures function as scaffolds capable of housing the immature mouse eggs until they are ready to be released and fertilized. They provided the maturing follicles with structural support, like the scaffolds on a building. The diamond-like shape was essential to preserve the spherical follicles, Laronda noted.

“The follicles seemed to really like something that felt snug,” she said, “but gave them room to grow.”

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The research team had been studying different scaffold models for a long time, and they were thrilled when their newest experiment worked.

“The live birth was the most exciting for us,” Laronda recalled. “It was just so prominent and clear that it worked when you have a live pup there.”

The next step is to continue testing this scaffold system in animal models, and eventually in humans. The advantage of using 3D printing, said Laronda, is that “we could easily scale up and adjust to what human follicles would need.”

Human trials remain a distant prospect for now, but the research team hopes their work will eventually be able to help women with diminished reproductive systems through all stages of their lives, from puberty to menopause.

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