Apr 1, 2016 

Scientists from Northwestern University have created 3D printed ovary implants that could one day restore fertility and hormone function in women who have survived childhood cancer or were born with reduced ovarian function and are experiencing infertility as a result.

The researchers tested the 3D bioprinted ovary implants in mice, who had had their original ovaries removed, and found that following the procedure, the mice were able to ovulate, give birth and even nurse their healthy young. The work is the first of its kind to demonstrate well-defined 3D printed scaffolds as an artificial environment for supporting follicle health and growth.

Data suggests that up to 12% of all people—men and women—are affected by infertility. While there are many possible causes, most cases of female infertility arise from an inability to produce eggs (oocytes), a function that occurs in the ovaries.

In particular, woman who have undergone chemotherapy or other radiation therapies, or who were born with developmental disorders, can suffer the “harsh consequences of gonadal toxicity,” resulting in infertility, hormone insufficiency, and even the inability to go through puberty.

Current female infertility treatments in these cases are quite limited. On the one hand, autotransplants of preserved ovarian tissue can be used to give patients short-term hormone cycling and live birth, however they possess a short life span and can increase the risk of cancer in the patient.

According to the Northwestern researchers, another option involves using biomaterials, such as hydrogels, however existing methods do not permit “advanced design to optimize transplant function.”

The team of endocrinologists  thus turned to 3D bioprinting as a flexible design tool for on-demand scaffold building, to develop a 3D printed artificial ovary for long-term fertility and hormone health options.

“One of the biggest concerns for patients diagnosed with cancer is how the treatment may affect their fertility and hormone health,” said Monica M. Laronda, PhD, a postdoctoral research fellow at Northwestern University’s Feinberg School of Medicine and lead author in the study. “We are developing new ways to restore their quality of life by engineering ovary bioprosthesis implants.”

Using an EnvisionTEC 3D bioplotter, the scientists carefully assembled 3D printed scaffolds from a gelatin material that can support hormone-producing cells (in addition to producing eggs, the main function of the ovaries is to produce the female hormones estrogen and progesterone).

An important consideration was to ensure that the 3D printed scaffolds were rigid enough to be handled during surgery, while providing enough space for oocyte growth, blood vessel formation, and ovulation to occur.

Once the criss-crossing structure of the 3D scaffold was assembled, the scientists seeded them with ovarian follicles—that is, the cellular aggregation where the egg and hormones are actually produced.  Together, the 3D printed gelatin scaffold and ovarian follicles create an artificial ovary bioprosthetic.

To test these ovaries, the scientists removed ovaries from living mice and implanted the 3D printed versions. Not only did they find that the mice were able to carry their young to term, but the prosthetic ovaries also restored their natural hormone cycles. The researchers further reported that follicles with two or more scaffolds resulted in a 82.8% survival rate, and that the follicles remained viable within the 3D printed gelatin scaffolds for as long as eight days.

Finally, the 3D printed scaffold structure demonstrated the ability to support the growth of blood vessels in mice without the need for additional substances to stimulate the process, a finding that could pave the way for 3D printed transplant studies more generally.

“We developed this implant with downstream human applications in mind, as it is made through a scalable 3D printing method, using a material already used in humans,” said Laronda. “We hope to one day restore fertility and hormone function in women who suffer from the side effects of cancer treatments or who were born with reduced ovarian function.”

The research, titled “Bioengineering an Artificial Ovary with 3D Printing,” was conducted by the Simpson Querrey Institute for BioNanotechnology at Northwestern University, and will be presented at the Endocrine Society’s annual meeting, ENDO 2016, taking place in Boston this weekend.

Scientists are also investigating whether 3D printing technology can help solve male infertility, as with the 3D printed Spermbots research underway in Germany.




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