3D printed ovaries produce healthy offspring

Infertile mice produced healthy pups when their ovaries were replaced with 3D printed prosthetics.

For women who can no longer give birth because of a disease or treatment, 3D printable ovaries could one day restore fertility and boost hormone production. In a new Nature Communications study, researchers have taken a big step in that direction by successfully restoring ovarian hormone and egg production in sterilized mice. Researchers removed the mice’s ovaries and replaced them with 3D printed bioprosthetic ovaries made from gelatin, enabling the mice not only to ovulate, but also give birth to healthy mouse pups.

We spoke with one of the study’s authors, Monica M. Laronda of the Ann & Robert H Lurie Children’s Hospital and Northwestern University, about the study.

ResearchGate: What motivated this study?

Monica Laronda: Creating an engineered ovary was motivated by the need to restore hormone function and the option of fertility in young girls or women whose ovaries are affected by disease or treatments. The ovarian follicles are dynamic, so we needed a dynamic scaffold structure. We sought the help of materials scientists and 3D printing experts in the Shah Lab to helps us address these fundamental tissue-engineering feats.

RG: What did you develop?

Laronda: We developed a bioprosthetic ovary, a combination of ovarian follicles that are supported by a 3D printed scaffold that together is transplanted to restore ovarian hormone and egg production. We restored ovarian function with this bioprosthetic ovary in sterilized mice.

RG: Can you give us a brief insight into how you achieved this?

Laronda: We used 3D printed scaffolds made of gelatin to support ovarian follicles. We transplanted this bioprosthetic ovary into mice, in the same location where their natural ovaries were. We identified follicle growth and vessel infiltration and found that the transplant produced steroid and peptide hormones and could ovulate and support a pregnancy that resulted in healthy pups.

RG: What were some of the challenges you faced? How did you overcome them?

Laronda: We needed the spherical follicle to be supported enough to maintain the connections between the hormone-producing support cells and the centralized oocyte (potential egg cell), but dynamic enough to accommodate the expansion of large preovulatory follicles and ovulation of an egg. We also needed this scaffold to be durable enough to support handling during transplant, and porous to allow nutrient exchange and vessel infiltration. We tested different architectural designs using precise 3D printing techniques to best extrude gelatin and give us a scaffold that would meet these criteria.

RG: How close are we to a human trial?

Laronda: There are still some key steps that are needed to safely try this in humans. We need to do a number of things: test this scaffold material and design with human follicles, create a bioprosthetic ovary in a large animal model, and create clinical-grade scaffolds.

RG: Can you tell us more about the 3D printing used for this study?

Laronda: 3D printing is scalable and can tailor the scaffold for specific tissue spatial, biochemical, and mechanical cues. We chose gelatin as a material because it is relatively cheap and already has several FDA-approved uses, which can facilitate the translation of our 3D printable gelatin devices for clinical use. Gelatin is a derivative of collagen, the most abundant type of matrix proteins in most organs, including the ovary. The 3D printed design nurtured the ovarian follicles, allowed for nutrient and endocrine (hormone) exchange, and expansion and release of a fertilizable egg.

RG: What’s next for your research?

Laronda: The Woodruff Lab will continue to define what it means to be a healthy human egg and investigate ways to protect the potential egg cells. The Laronda Lab is expanding on this published research in larger animal models.

Featured image courtesy of Seán Ó Domhnaill.