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Biomaterials Core*
Site: Northwestern University
Principal Investigator: Lonnie D. Shea, PhD
Rationale
For folliculogenesis to properly occur, it is essential to maintain the intimate physiological connections between the oocyte and surrounding somatic cells. To recapitulate the 3-dimensionality of the ovary and maintain the appropriate size, shape, and architecture of the ovarian follicle while providing the necessary stimuli to direct cellular responses, a synthetic scaffold must serve as an in vitro mimic of the in vivo ovarian microenvironment.
Previous work has demonstrated that the hydrogel alginate phenocopies the in vivo ovarian environment by maintaining follicular architecture and permitting combinations of diffusible, insoluble, and mechanical signals to influence the development of the follicle. Using this scaffold, murine ovarian follicles have been successfully matured in vitro to yield high-quality oocytes that were fertilized and used for the birth of live, viable offspring.
The application of biomaterials and tissue engineering to reproductive biology provides an enabling technology that is central to the Oncofertility Consortium. The work of the biomaterials core directly supports the work of other Consortium members; in particular, growth of large nonhuman primate and human follicles that may have different requirements from mouse follicles, maintaining follicle architecture and facilitating handling during cryopreservation, and promoting engraftment and survival of primate follicles following autotransplantation of ovarian tissue. The objectives of this project are to:
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Provide biomaterial support to the Oncofertility Consortium
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Identify biomaterial properties and culture conditions to maximize primate follicle growth and transfer knowledge to appropriate projects
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Develop novel biomaterials that can be used to minimize tissue cryoinjury
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Engineer drug-releasing hydrogels to optimize ovarian cortical strip transplants
Key Experiments
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Assess the mechanical influence of the ovarian stroma on follicle development using the alginate culture system
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Perform thermal analysis and polymer molecular weight measurements before and after follicle cryopreservation to identify optimal alginate properties and cooling procedures for maximum survival of individual follicles and cortical strips
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Subcutaneously implant alginate hydrogels with immobilized ECM and angiogenic factors into the abdomen of mice and analyze cellular infiltration, identify cell types, and quantify blood vessel growth (vascularization) to gauge host tissue engraftment
Consortium Support and Impact
The Biomaterials Core provides critical service, support, and training to the other Consortium projects. The exchange of biomaterials, development of techniques, training, and constant communication are central to the Core’s mission. In addition, there is reciprocal interaction as results from the individual projects feed into the Core to further optimize 3-D culture systems.
