Figure 1. A scientist holds a bioprosthetic mouse ovary made of gelatin with tweezers.(1)

One of the scientific advances made in recent years is 3D printing of human organs. The creation of an organ from a suitable material often allows medical doctors to decide on the best way to perform a surgical procedure. In addition, it opens up new possibilities for the use of 3D printing technologies in organ transplant programs. Now, researchers from Northwestern University Feinberg School of Medicine and McCormick School of Engineering have developed prosthetic ovaries made of gelatin, which allowed mice to conceive and give birth to healthy offspring.

The bioprosthetic ovaries are constructed of 3D-printed scaffolds that house immature eggs, and have been successful in boosting hormone production and restoring fertility in mice. The material used for building up these ovaries is a biological hydrogel made from decomposed collagen naturally found in animal ovaries. This material is degradable to allow cellular remodelling, contains cell adhesion sites and shows soft durable mechanical properties. Scientists built the ovaries by printing various patterns of overlapping gelatin filaments on glass slides. Modulating the distance between these filaments, as well as the advanced angle between layers, allowed for the generation of different pore sizes and geometries.

The ovaries are referred to as “bioprosthetic” organs because they contain both living material (ovarian cells) and nonliving material (gelatin). They release hormones in the same way a normal ovary would, allowing the animal to go through its natural cycle, including ovulation. Also, this scaffolding needed to be made of organic materials, stiff enough to be handled during surgery and sufficiently porous to interact naturally with the tissues of the mouse body. In the study, after having placed the biosynthetic ovaries in the mouse, 40-50 follicles were carefully implanted into each scaffold.

Vascularization in the ovary is critical because it provides oxygen and nutrients to the follicles, and because it allows follicle-produced hormones to circulate in the blood stream. Since gelatin is a natural material, the body can recognize the implant as a regular body part and allows blood vessels to grow into it.

Although mice had been sterilized by the removal of both ovaries, the reproductive tract (including the oviduct), had been left intact to assess fertility through natural mating after the surgical introduction of the 3D-printed organs. The study culminated in the pairing of a dozen female mice, two mice with sham controls (bioprosthetic ovary without follicles) and seven mice with bioprosthetic ovaries were mated with males who had previously sired pups. Three bioprosthetic ovary recipients had litters of one or two pups each, while none of the sham controls had pups. In all cases, the mothers produced milk to feed them.

FUTURE APPLICATIONS IN HUMANS

Researchers hope in particular to help cancer survivors whose treatments had damaged their ovaries. The 3-D printed bioprosthetic scaffold can be repopulated using patient’s previously extracted own follicles or donated samples from ovarian tissues. Another possible use would be helping women with impaired ovaries, so that symptoms of menopause could be alleviated. Rather than using synthetic hormones, which often entail unpleasant side effects, women could have an all-natural source of hormones implanted directly into her body.

The team is now preparing a similar trial on pigs, which are closer to humans in size and biology. They believe that it might be a challenge to scale up the 3D-printed structure to the size needed for human use.

REFERENCES

Original publication: Laronda MM, Rutz AL, Xiao S, Whelan KA, Duncan FE, Roth EW et al. A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice. Nat Commun. 2017; 8:15261.

1. Available from: http://www.npr.org/sections/health-shots/2017/05/20/528646323/scientists-one-step-closer-to-3-d-printed-ovaries-to-treat-infertility. [Cited 22 May 2017].