# In Vitro Growth of Human Follicles: Current and Future Perspectives

## TL;DR

This paper reviews current methods for growing human ovarian follicles in the lab, highlighting the potential of Organ-on-a-Chip technology to improve fertility preservation.

## Contribution

The paper provides a critical review of in vitro follicle culture systems, emphasizing the promise of Organ-on-a-Chip technology.

## Key findings

- Traditional 2D culture systems fail to support follicle survival and mimic ovarian mechanics.
- 3D and biomimetic models are gaining attention for better follicle development.
- Organ-on-a-Chip technology shows promise for follicle cultivation and maintenance.

## Abstract

Ovarian tissue cryopreservation is gaining importance as a successful method to restore fertility to girls and young women at high risk of sterility. However, there are concerns regarding the safety of transplantation after ovarian tissue cryopreservation due to the high risk of reintroducing cancer cells and causing disease recurrence. In these cases, the development of culture systems that support oocyte development from the primordial follicle stage is required. Notable achievements have been reached in human follicle in vitro growth in the past decade. Currently, systems for the in vitro culture of ovarian tissue are based on two-dimensional substrates that do not support the survival of follicles or recapitulate the mechanical heterogenicity in the mammalian ovary. Recognition of the importance of special arrangements between cells has spurred research in three-dimensional culture systems, and the provision of a precise culture system that maximizes the diffusion of nutrients and gases through the follicles has raised interest in advanced biomimetic models. The current review critically examines various culture systems employed for the in vitro development of follicles, with a particular focus on solutions utilizing Organ-on-a-Chip (OOC) technology. The emphasis on OOC technology underscores its role as a promising avenue in ensuring the successful cultivation and maintenance of follicular structures during the culture period.