A team from Northwestern University created bioprosthetic ovaries that ultimately led to the restoration of hormone production and fertility in mice.

The implant features a combination of ovarian follicles and a 3D-printed scaffold, or skeleton, that houses the immature eggs. The follicles, seeded in scaffolds of varying architectures, resulted in the live birth of mouse pups.

Tech Briefs spoke with researcher Ramille Shah about the scientists’ achievement — and the future of bioprinting.

Dr. Ramille Shah, assistant professor of materials science and engineering at Northwestern’s McCormick School of Engineering, and of surgery at the Northwestern University Feinberg School.

Tech Briefs: What did your research accomplish?

Dr. Ramille Shah: This is the first 3D-printed artificial scaffold with follicles that has resulted in recovery of hormone function in a mouse model, and has led to live birth. It’s an advancement not just in tissue engineering and 3D printing, but also in the field of fertility preservation. It really can lead to a new solution for patients who are surviving cancer, especially pediatric patients who want to maintain their ability to have normal hormone function, as well as eventually give birth.

Tech Briefs: What makes up the bioprosthetic ovary?

Shah: The combination of the scaffold and the follicle are what we consider the bioprosthetic ovary. The follicles are the components of the ovary that lead to egg fertilization and hormone production. The follicle is made up of the egg surrounded by support cells that are responsible for producing the normal hormones in a woman.

Tech Briefs: What kinds of materials or inks were used to create the scaffold?

Shah: Interestingly, it was just gelatin. The gelatin had been chosen for this particular case because it is derived from collagen, which is the main protein in our bodies. Cells easily recognize it, it’s degradable, and cells can remodel it.

We created very-well-defined, thicker structures with the gelatin by controlling the printing temperature. We found the optimal temperature that allowed us to print and maintain that structure after printing so that it doesn’t just puddle up into a pool.

Tech Briefs: What was your development “strategy?”

Shah: I realize that no manmade materials can recapitulate what the body naturally does. We are trying to provide the simplest signals to these cells to induce those cells to then remodel that simple printed scaffold and deposit the right kind of matrix that is normally found in the body. That’s the whole goal of tissue engineering: to provide an artificial environment, and then over time it degrades and gets replaced by natural tissue.

Tech Briefs: What’s next? What will you be studying?

Shah: This demonstrated live birth, but what we don’t know yet is how long this artificial ovary can be maintained in the body. Does it survive multiple cycles? Can it lead to multiple births over time? That’s something we still need to study and optimize.

A lot of signaling is incorporated within the extracellular matrix itself in that organ. So, we’re trying to harness that bioactivity and incorporate those types of materials into our inks, as well as [incorporate] different components that can also influence cells such as other proteins and growth factors that enhance cell survival, proliferation, or function. There are different ways that you can tailor these materials. Now it’s about: Can we incorporate these elements but still maintain the printability?

Tech Briefs: How do you ensure that implanted structures integrate well with the body?

Northwestern University researchers used a 3D printer and gelatin to create the bioprosthetic ovary. (Image Credit: Northwestern University)

Shah: One of the main challenges in the tissue engineering field is vascularization, or blood vessel formation, within the implant. Without blood vessel integration, cells within the scaffold do not get the sufficient nutrients needed for survival.

In the case of the artificial ovary, we know that the “Scaffold 1.0” works because, after the live birth, the mother started to lactate. That lactation was able to happen because the implant’s follicles were still alive and were producing the hormones that lead to lactation.

For the hormone to be dispersed systemically to trigger lactation, you needed to have those blood vessels in there, so the hormone is being sufficiently transported from that implant into the rest of the body.

Tech Briefs: Do you ultimately see this being used in humans?

Shah: Oh, yes, absolutely. That’s our ultimate goal. And this can come in different stages. The first use doesn’t necessarily have to be to completely replace the ovary to lead to live birth. I think the many steps towards that would be first to use it as a more natural way for hormone replacement. It makes a huge impact on the overall health of a woman if she doesn’t have normal hormone production, including cardiovascular health, bone health, and memory.

Tech Briefs: Where do you envision bioprinting being used in the future?

Shah: 3D printing is being used mainly for surgical guides and metal implants, such as patient-specific hip or knee implants. 3D printing is also used for creating models for surgical preparation; you create models, and they can plan the surgeries so that they go more smoothly. I think, in the future, you’ll see more examples of how the process can help to regenerate damaged tissues — really transforming the tissue engineering field and accelerating it to something that can be used clinically.

For more information, visit news.northwestern.edu.


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What do you think? What kinds of bioprinting possibilities do you envision? Send us your comments below!