We are a step closer to engineering replacement ovaries for humans, after mice with 3D printed ovaries have successfully given birth to healthy pups. The experiment, carried out by researchers at the Feinberg School of Medicine at Northwestern University, implanted the mice with bioprosthetic ovaries made from gelatin. They published their results in Nature.
Could 3D-printed organs be medicine’s next grisly black market?
Tissues, organs and even bones have been 3D printed in the past. In one case, a tiny replica of a liver was generated from living cells. Today, these kinds of bioengineered materials are sufficient for safer lab testing of new drugs. However, the successful implantation of bioprosthetic ovaries points to some exciting future developments for the field.
The key, the authors told WIRED, was to design a structure firm enough to survive the implantation procedure and hold the mice follicles containing immature eggs and hormones, but porous enough for it to function and become embedded in the blood supply. “[Gelatin] is relatively cheap, has already been approved by our FDA for several uses in the in clinic, and because it is derived from collagen, one of the most abundant structural proteins of the ovary,” says coauthor Monica Laronda.
The gelatin was 3D-printed into 15mm x 15mm overlapping strips that made up a scaffold-like structure. The mouse follicles were then introduced, and after the team found both the follicles and eggs would survive for more than a week, they decided to implant them. Seven mice had their ovaries surgically removed, before bioprosthetic ovaries filled with around 50 follicles were implanted in their place. Because of the porous nature of the gelatin, blood vessels were able to integrate, keeping the ovary ‘alive’ and helping hormones from the follicles circulate the mouse’s body.
Three of the mice became pregnant after mating and gave birth to healthy pups. As a result of the hormones circulating these mice, they were also able to produce milk.
“Our longest transplants were in the recipient mouse for 11 weeks and there were still follicles present when we analysed it,” says Laronda.
The team plans on following up the study by expanding the trial to larger animals, and designing clinical-grade scaffolds. “We need to make sure what we have done will translate into humans. One way we are tackling that is to see if we can repeat this in a larger animal model,” says Laronda. “We are also going to investigate the 3D printed design and materials on human ovarian follicles in culture.”
For professor Daniel Brison, scientific director of the department of reproductive medicine at Old St Mary’s Hospital, the breakthrough finding is the scaffold technique, which allowed the eggs to survive for so long.
“The [technique] allows the researchers to choose exactly the right physical structure to support the follicles – a bit like designing the perfect egg box to carry eggs without breaking them,” says Brison. “But in this case the egg box or ‘follicle box’ also allows the follicles to grow, mature and produce healthy eggs.”
Ultimately, the aim is to create a bioprosthetic ovary that could entirely replace the function of a dysfunctional ovary in a human.
“We foresee this being especially useful for those pediatric patients who have a disease or disease treatment that would affect their ovaries,” says Laronda. “Prior to the detrimental effects of the disease or disease treatment we would isolate and freeze their ovarian tissue to preserve the follicles – potential egg cells surrounded by the steroid-producing cells – and then transplant them back in, within the 3D printed scaffolds, once the woman is ready to conceive or requires hormone restoration.”
But if the ovary could only exist temporarily, as in the mice, living off the hormones implanted during the procedure, would it really be preferable to IVF? Brison believe the benefits would be worth it:
“Natural conception in the body avoids all of the complications of IVF – the expense, multiple attempts required, the risk of multiple pregnancy, the small risk to the IVF child of being conceived outside of the body,” says Brison. “The other important advantage of having a transplanted ovary, of this new type, or by having frozen ovarian tissue transplanted using existing methods, are that the woman has normal hormonal cycles.”
Further study is needed, Brison says, to understand the implications of the new procedure and any risks involves. “The reason we don’t understand the risks is that natural reproduction has evolved over millions of years, whereas new reproductive technologies have only been around for a few decades.”