New 3D-Printed Ovaries Have Allowed Infertile Mice to Give Birth

Infertile mice have been given the ability to birth healthy offspring, thanks to new 3D-printed ovaries that connected with the animals' blood supply in just one week, and started releasing eggs.

Researchers now plan on testing these artificial ovaries in pigs, and if all goes well, human trials will follow. It's hoped that the lab-made organs will one day be an option for women with reproductive systems that have been damaged by cancer treatments.

"This research shows these bioprosthetic ovaries have long-term, durable function," says one of the team, reproductive scientist Teresa K. Woodruff, from Northwestern University.

"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."

Woodruff and her team produced the artificial ovaries by using gelatin as the 'ink' in the 3D printer - a type of biological hydrogel that's less likely to be rejected by the body, and also porous, which helps it interact with the host's tissues and blood supply.

Hydrogels are a mixture of 99 percent water and a little bit of polymer, which means they can tend to be quite soft, but the Northwestern team was able to manipulate their gelatin ink to give it a flexible but firm quality.

"Most hydrogels are very weak, since they're made up of mostly water, and will often collapse on themselves," says one of the researchers, Ramille Shah.

"But we found a gelatin temperature that allows it to be self-supporting, not collapse, and lead to building multiple layers. No one else has been able to print gelatin with such well-defined and self-supported geometry."

It sounds simple enough, but the survival of the organs depended wholly on the specific patterning of the pores in the 3D-printed scaffolding. Each hole had to be strategically placed within the various lattice layers to hold dozens of working follicles - the sacs that contain immature egg cells - and allow them to grow.

"You have to house both the small ones and the large ones, and you have to have an environment that can provide cross-talk between these follicles, because that's how the natural ovary signals for only specific ones to ovulate," Shah told CNN.

The pores also had to be arranged to ensure the right amount of blood flow through the artificial ovaries.

The team says this is the first study to demonstrate just how crucial this patterning is to ensure the long-term success of artificial ovaries.

The organs were transplanted into female mice that had ovaries surgically removed, and of the seven that mated after the implant, three gave birth to litters of offspring. All three litters - which each included at least two pups - were robust and healthy.

The mothers were also able to lactate, which means their hormone signals were still in working order after having their natural ovaries removed.

Of course, it's all well and good for infertile mice, but when will the technology start to make a difference in human lives?

The team is hoping to scale up their artificial ovary 'pattern', and 3D-print larger versions for infertile pigs. If all goes well, they plan on introducing the technology to human patients gradually, starting with structures that only substitute hormone production, before working towards fully functioning artificial organs.

This would be especially important in young cancer patients, who are yet to go through puberty, and need their artificial ovaries to grow with them.

"What happens with some of our cancer patients is that their ovaries don't function at a high enough level and they need to use hormone replacement therapies in order to trigger puberty," one of the team, Monica Laronda, said in a statement.

"The purpose of this scaffold is to recapitulate how an ovary would function. We're thinking big picture, meaning every stage of the girl's life, so puberty through adulthood to a natural menopause."

We've got some years to wait before we see this progress to human trials, but hopefully this is the start of something revolutionary.

As Anthony Atala from the Wake Forest Institute for Regenerative Medicine, who wasn't involved in the study, told CNN, the ability to be able to 3D-print replica organs would make a huge difference in the future, because once the pattern is just right, it should be easy to scale and reproduce.

"The printing gives you scalability, because you can scale a technology up instead of making them by hand, it gives you reproducibility, because you can print them in the same manner every time, and it gives you precision, because it can precisely place the cells where you need them," said Atala.

"It will eventually decrease the cost of the production of these technologies, because you're automating the process."



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