Engineering complex, heterogeneous ovarian microenvironments

Gargus, Emma S

doi:https://doi.org/10.21985/n2-69fm-tj36

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Engineering complex, heterogeneous ovarian microenvironments

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Current biomaterials-based methods for in vitro ovarian follicle culture enable individual follicles or follicle classes to survive and carry out basic functions of the ovary, including hormone and release of mature oocytes upon gonadotropin stimulation. However, these current strategies do not support the survival and maturation of isolated primordial and primary follicles, nor do they recapitulate the recurring monthly hormone cycles that characterize human ovarian function. We hypothesize that these limitations are the result of the reductionist nature of current biomaterials approaches, which eliminate the complexity of the natural ovary. Thus, the studies herein aim to characterize the structure-property relationships that underlie ovarian function and to develop novel biomaterials for ovarian tissue engineering that mimic the biochemical and physical properties of the natural ovary. Using shear wave ultrasound elastography, we identified spatial patterns in the distribution of shear wave velocities in intact, ex vivo bovine ovaries, indicating a relationship between tissue structure and mechanical properties. We also report, for the first time, a quantifiable difference in mechanical properties between the ovarian cortex and medulla. Next, we developed a family of cell-friendly, mechanically-tunable bioinks based on partial poly(ethylene gycol) (PEG) cross-linking. These bioinks can be used for 3D printing complex, multi-material, cell-laden structures with spatio-temporally heterogeneous mechanical properties. Finally, we processed decellularized ovary into a tissue-specific hydrogel can be used as a 2D substrate for ovarian cell culture or a 3D matrix for follicle encapsulation. Taken together, these studies lay a foundation for the next-generation 3D printed ovarian bioprosthetic that will advance our understanding of ovarian physiology and expand therapeutic options for women.

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