May 16, 2017

Scientists at the Oregon National Primate Research Center (ONPRC) have shown that prosthetic ovaries made of gelatin allow 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,” said Dr. Mary Zelinski, a reproductive scientist at ONPRC.

The researchers used a 3D printer with a nozzle that sprayed 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. The team then carefully inserted mouse follicles into these “scaffolds.” The scaffolds that were more tightly woven had a higher percentage of surviving follicles after eight 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 pieces of ovarian tissue containing 40 to 50 follicles into each one, creating a “bioprosthetic” ovary. They then surgically removed the ovaries from seven mice and put 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.

After the mice mated, three of the seven females gave birth to healthy litters. The mice that gave birth also lactated naturally, demonstrating 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.

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