Abstract
The female reproductive tract (FRT) is a complex system comprising multiple interacting organs with a variety of functions that has traditionally been studied with 2-D in vitro cell cultures and animal models, including for nanomedicine research. Limitations of these models including failure to recapitulate 3-D tissue architecture in vitro and human physiology in vivo have motivated the development of new approach methodologies (NAMs). Recently, NAMs to design 3-D in vitro culture systems to model the FRT have seen expanded application. While these non-animal models have been employed to explore therapeutic delivery, they remain underutilized in the field of nanomedicine targeting delivery to the FRT. This review summarizes advances in 3-D in vitro NAM models of the FRT reported over the past decade in the research literature, including multi-cellular co-cultures, organoids, and organ-on-a-chip (OOC) methodologies to represent in vivo tissue as well as microfluidics to simulate transport, with the goal to highlight opportunities for design of effective nanomedicine targeting the FRT. Despite limitations, NAMs offer new horizons in nanomedicine research focusing on the female reproductive system. Further development of these methodologies for high-throughput applications is anticipated to open the next chapter in nanomedicine targeting the FRT.