The application of biomaterials and tissue engineering to reproductive biology provides an enabling technology underlying the development of the Oncofertility Consortium. A core is being developed for the translation of this technology.This proposed core has two major missions: i) research to further develop this enabling technology identify conditions for cryopreserving and maturing primate ovarian follicles, ii) service to provide materials and training to satellite locations for the maturation procedures. Previous work has demonstrated that the hydrogel alginate phenocopies the in vivo environment by maintaining follicular architecture while presenting a combination of diffusible, insoluble, and mechanical signals that combine to influence the development of the follicle. Ovarian follicles can be matured in vitro to yield high quality oocytes that can be fertilized and support live births with mice. The research objectives of this project are motivated by the need to develop hydrogels that i) support the growth of the large primate follicles that may have different requirements from mouse follicles, ii) maintain the follicle architecture and facilitate handling during cryopreservation, and iii) promote engraftment and survival of transplanted follicles following transplantation. The activities of this core are thus focused on four specific goals. Goal 1: Provide biomaterial support to the oncofertility consortium (R01A, R01B, R01C, P30A). Goal 2: Identify biomaterial properties and culture conditions that will maximize primate follicle growth, which will be translated to R01B and R01C. Goal 3: Develop novel biomaterials that can be used to minimize tissue cryoinjury for translation to R01A and P30B. Goal 4: Engineer drug-releasing hydrogels to optimize cortical strip transplants (R01B). An exciting team of investigators has been assembled towards translating novel technologies towards a significant clinical problem. Importantly, the generation of fertilizable oocytes and healthy embryos can immediately be translated clinically given the existing infrastructure for in vitro fertilization.

Agency
National Institute of Health (NIH)
Institute
National Institute of Biomedical Imaging and Bioengineering (NIBIB)
Type
Linked Center Core Grant (PL1)
Project #
5PL1EB008542-05
Application #
8114123
Study Section
Special Emphasis Panel (ZRR1-SRC (99))
Program Officer
Zullo, Steven J
Project Start
2007-09-01
Project End
2013-06-30
Budget Start
2011-07-01
Budget End
2013-06-30
Support Year
5
Fiscal Year
2011
Total Cost
$467,680
Indirect Cost
Name
Northwestern University at Chicago
Department
Engineering (All Types)
Type
Schools of Engineering
DUNS #
160079455
City
Evanston
State
IL
Country
United States
Zip Code
60201
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Xu, Jing; McGee, Whitney K; Bishop, Cecily V et al. (2015) Exposure of female macaques to Western-style diet with or without chronic T in vivo alters secondary follicle function during encapsulated 3-dimensional culture. Endocrinology 156:1133-42
Rodrigues, J K; Navarro, P A; Zelinski, M B et al. (2015) Direct actions of androgens on the survival, growth and secretion of steroids and anti-Müllerian hormone by individual macaque follicles during three-dimensional culture. Hum Reprod 30:664-74
Shea, Lonnie D; Woodruff, Teresa K; Shikanov, Ariella (2014) Bioengineering the ovarian follicle microenvironment. Annu Rev Biomed Eng 16:29-52
Tagler, David; Makanji, Yogeshwar; Tu, Tao et al. (2014) Promoting extracellular matrix remodeling via ascorbic acid enhances the survival of primary ovarian follicles encapsulated in alginate hydrogels. Biotechnol Bioeng 111:1417-29
Woodruff, Teresa K (2013) From the bench to bedside to babies: translational medicine made possible by funding multidisciplinary team science. J Assist Reprod Genet 30:1249-53
Ahn, Richard W; Barrett, Susan L; Raja, Meera R et al. (2013) Nano-encapsulation of arsenic trioxide enhances efficacy against murine lymphoma model while minimizing its impact on ovarian reserve in vitro and in vivo. PLoS One 8:e58491
Xu, J; Lawson, M S; Yeoman, R R et al. (2013) Fibrin promotes development and function of macaque primary follicles during encapsulated three-dimensional culture. Hum Reprod 28:2187-200
Tagler, David; Makanji, Yogeshwar; Anderson, Nicholas R et al. (2013) Supplemented ?MEM/F12-based medium enables the survival and growth of primary ovarian follicles encapsulated in alginate hydrogels. Biotechnol Bioeng 110:3258-68
Xu, Jing; Xu, Min; Bernuci, Marcelo P et al. (2013) Primate follicular development and oocyte maturation in vitro. Adv Exp Med Biol 761:43-67

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