New approach methodologies to model the female reproductive tract: advances and opportunities for nanomedicine

Introduction 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.Areas covered 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.Expert opinion/commentary 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.