The creation of artificial ovaries for humans is a step closer after birth of healthy pups from mice given ‘ovarian bioprosthesis’
Infertile mice have given birth to healthy pups after having their fertility restored with ovary implants made with a 3D printer.
Researchers created the synthetic ovaries by printing porous scaffolds from a gelatin ink and filling them with follicles, the tiny, fluid-holding sacs that contain immature egg cells.
In tests on mice that had one ovary surgically removed, scientists found that the implants hooked up to the blood supply within a week and went on to release eggs naturally through the pores built into the gelatin structures.
The work marks a step towards making artificial ovaries for young women whose reproductive systems have been damaged by cancer treatments, leaving them infertile or with hormone imbalances that require them to take regular hormone-boosting drugs.
“Our hope is that one day this ovarian bioprosthesis is really the ovary of the future,” said Teresa Woodruff at Northwestern University in Chicago. “The goal of the project is to be able to restore fertility and endocrine health to young cancer patients who have been sterilised by their cancer treatment.”
Of seven mice that mated after receiving the artificial ovaries, three gave birth to pups that had developed from eggs released by the implants. The mice fed normally on their mother’s milk and went on to have healthy litters of their own later in life.
Writing in the journal Nature Communications, the scientists describe how they printed layered lattices of gelatin strips to make the ovary implants. The sizes and positions of the holes in the structures were carefully controlled to hold dozens of follicles and allow blood vessels to connect to the implants. Mature eggs were then released from the implants as happens in normal ovulation.
Chemotherapy and high doses of radiation used in cancer treatment can destroy some or all of a woman’s eggs, putting them at risk of infertility and an early menopause. And while doctors have had some success in restoring women’s fertility from frozen ovarian tissue, an implant could potentially help those who do not bank healthy tissue when they are children.
Monica Laronda, a co-author on the study, said that an ovary implant could also help cancer survivors whose eggs are so damaged that they need hormone replacement therapy to trigger puberty. “We’re thinking big picture, meaning every stage of the girl’s life, so puberty through adulthood to a natural menopause,” she said.
A microscopic image of an immature mouse egg, surrounded by supportive cells, after it has been housed in a bioprosthetic ovary scaffold for six days. Photograph: Northwestern University
Scientists have made artificial ovaries for mice before, but the latest research is believed to be the first time that researchers have used 3D printing to manufacture them. It is not clear if the same approach will work in people because human follicles are much larger and grow rapidly until they are visible to the naked eye.
Other animal experiments performed nearly a decade ago hinted that women who had ovarian tissue transplants later in life might enjoy broader benefits from the procedure than restored fertility. In 2010, scientists at Kato Ladies Clinic in Tokyo found that ovarian transplants extended the lives of old mice, and led older females, who were normally inactive, to seek out mates and have babies. The researchers conceded that far more work was needed to assess the effects in women.
Advances in 3D printing have already transformed some areas of medicine by allowing the doctors to make bespoke body parts that can be directly implanted into patients. Last year, South Korean surgeons printed a titanium heel bone for a man who had a tumour removed from his foot.
Meanwhile, researchers in North Carolina announced that they had made ears, jawbones and skeletal muscles by 3D printing structures laced with living cells. Other groups have printed vascular networks that will be vital for creating large synthetic organs in the lab.