A bioprosthetic ovary created using 3D printed microporous scaffolds restores ovarian function in sterilized mice

Abstract

Emerging additive manufacturing techniques enable investigation of the effects of pore geometry on cell behavior and function. Here, we 3D print microporous hydrogel scaffolds to test how varying pore geometry, accomplished by manipulating the advancing angle between printed layers, affects the survival of ovarian follicles. 30° and 60° scaffolds provide corners that surround follicles on multiple sides while 90° scaffolds have an open porosity that limits follicle–scaffold interaction. As the amount of scaffold interaction increases, follicle spreading is limited and survival increases. Follicle-seeded scaffolds become highly vascularized and ovarian function is fully restored when implanted in surgically sterilized mice. Moreover, pups are born through natural mating and thrive through maternal lactation. These findings present an in vivo functional ovarian implant designed with 3D printing, and indicate that scaffold pore architecture is a critical variable in additively manufactured scaffold design for functional tissue engineering.

Breaking new ground on the ovary construction project

“…Spearheaded by the collaborations of Professor Marie-Madeleine Dolmans, these studies recognize the importance of building materials, in this case mixtures of fibrin tuned to exhibit the rigidity most similar to the native ovarian tissue. That the physical nature of the ovarian cortex was a telling determinant for growth and survival of follicles was first articulated here in JARG in a paper by Woodruff and Shea [2] whose continuing contributions to this field also exemplify the utility of engineering principles when modeling tissues and organs for purposes encompassed in the area of regenerative medicine [3].…”

Clinical Applications of 3D Printing

“…Bioprinting involves the use of various techniques, such as fused deposition modeling, to print bioactive scaffolds impregnated with growth factors designed to stimulate regeneration or drugs that concentrate their activity in the microenvironment, print customized bioactive implants and devices on demand, even generate customized living tissues (56-59, 101, 102). …”

“…Accurately replicating the architecture of blood vessels, connective tissue, and other supporting tissue in and about visceral organs are some of the biggest challenges faced by researchers. Although additive manufacturing has been used to construct organs and tissue implanted in mice and rats (101, 102), no 3D printed organ has yet been used in humans.…”

“…Laronda et al (101) created a bioengineered 3D printed ovary and implanted them in mice with bilateral oophorectomy. The 3D printed scaffold had stiffness that mimicked ovarian tissue and a porous morphology to accommodate ovarian follicles.…”

Educating an oocyte—the complex dialogue between mentor and mentee

“…And yet, we and our patients have been hearing about breakthroughs in the propagation of oocytes from stem cells and the elaboration of artificial ovaries using bioengineering principles that mimic some of the professorial principles employed during follicle development in vivo-at least in mice [6].…”