3D-printed ovaries restore fertility in mice

Fans of 3D printing say it has the potential to revolutionize medicine—think 3D-printed skin, ears, bone scaffolds, and heart valves. Now, prosthetic ovaries made of gelatin have allowed mice to conceive and give birth to healthy offspring. Such engineered ovaries could one day be used to help restore fertility in cancer survivors rendered sterile by radiation or chemotherapy.

This “landmark study” is a “significant advance in the application of bioengineering to reproductive tissues,” says Mary Zelinski, a reproductive scientist at the Oregon National Primate Research Center in Beaverton who was not involved with the work.

The researchers used a 3D printer with a nozzle that fired gelatin, derived from the collagen that’s naturally found in animal ovaries. The scientists built the ovaries by printing various patterns of overlapping gelatin filaments on glass slides—like building with Lincoln Logs, but on a miniature scale: Each scaffold measured just 15 by 15 millimeters. The team then carefully inserted mouse follicles—spherical structures containing a growing egg surrounded by hormone-producing cells—into these “scaffolds.” The scaffolds that were more tightly woven hosted a higher fraction of surviving follicles after 8 days, an effect the team attributes to the follicles having better physical support.

The researchers then tested the more tightly woven scaffolds in live mice. The researchers punched out 2-millimeter circles through the scaffolds and implanted 40–50 follicles into each one, creating a “bioprosthetic” ovary. They then surgically removed the ovaries from seven mice and sutured the prosthetic ovaries in their place. The team showed that blood vessels from each mouse infiltrated the scaffolds. This vascularization is critical because it provides oxygen and nutrients to the follicles and allows hormones produced by the follicles to circulate in the blood stream.

The researchers allowed the mice to mate, and three of the females gave birth to healthy litters, the team reports today in Nature Communications . The mice that gave birth also lactated naturally, which demonstrated that the follicles embedded in the scaffolds produced normal levels of hormones.

The team is hopeful that similar bioprosthetic ovaries can be implanted in human patients to restore fertility, using a patient’s own previously extracted follicles or donated samples. But that is a long way off. Ovarian scaffolds for humans will need to be specifically designed to host blood vessels because of their larger size, a challenge any large “printed” body part will have to overcome, says Nicolas Sigaux, a surgeon focused on medical applications of 3D printing at the Lyon-Sud Hospital Center in France. “Vascularization is the main limitation to printing large pieces of functional tissue.” Once this problem is solved, ready-to-implant organs should be possible with 3D bioprinting, he notes.