Premature ovarian insufficiency (POI) and infertility are irreversible and life-altering consequences of radiation and chemotherapy, significantly affecting young cancer survivors. Restoring reproductive function in women poses a unique challenge, as they are born with a finite and non-renewable reserve of ovarian follicles—the ovary’s functional units, each containing a single oocyte and hormone-producing somatic cells. Current clinical options for restoring lost ovarian endocrine function are limited to hormone replacement therapy (HRT), which provides only a subset of gonadal hormones in a continuous fashion, unlike the cyclical and pulsatile hormone patterns found in healthy young women.

To address these limitations, my lab has developed a cell-based therapy that delivers the full spectrum of ovarian hormones at physiological levels and rates, and is capable of responding to feedback from the body. This innovative therapy uses an immune-isolating hydrogel capsule with a degradable core and a non-degradable shell to encapsulate and implant donor ovarian tissue. The design enables growth and expansion of the ovarian grafts while effectively preventing immune cell infiltration. In studies with immunocompromised and immunocompetent ovariectomized mice, implantation of encapsulated human ovarian tissue successfully restored estrous cycles and produced systemic estradiol levels, correlated with the presence of large antral follicles in the grafts—results comparable to non-encapsulated controls.

Our research also aims to enhance in vitro ovarian follicle development. We have engineered biomimetic matrices that support the deposition and retention of extracellular matrix (ECM) molecules secreted by cultured follicles and cells, replicating the fibrous structure of native ECM to better support folliculogenesis.

Lastly, the engineering efforts in my lab are closely integrated with biological discovery. Recently, we published a high-resolution spatial cell atlas of the human ovary and sequenced individual oocytes from human primordial follicles by combining spatial transcriptomics with single-cell RNA sequencing. By profiling over 18,000 genes in carefully selected ovarian regions, we revealed localized gene expression patterns and distinct cellular architectures. This spatially resolved atlas, highlighting new molecular markers and structure–function relationships critical to fertility, hormone production, and ovarian aging, serves as a valuable resource to optimize biomimetic platforms for follicle growth both in vitro and in vivo. Ultimately, our research aims to advance cures for infertility and loss of ovarian function through innovative therapeutic approaches.