The Development of Microphysiological Systems for Reproductive Biology ApplicationsPublic
Microfluidic technologies enable multi-tissue culture and precise control of media exchange and therefore have significant potential to create more complex in vitro models of reproductive systems, including endocrine cycles. However, microfluidic technologies have largely been applied to gamete-level culture in reproductive biology, with very little progress in organ-level culture. Herein we detail the development a number of modular microfluidic platforms including the EVATAR, which includes murine ovarian follicles, human fallopian tube, uterine myometrium and endometrium, ectocervix, and liver spheroids. Using these platforms, we successfully phenocopy the 28-day ovarian hormone cycle with a 14-day follicular phase followed by a 14-day luteal phase. This is the first time five organs have been integrated for month-long experiments and maintained dynamic function. Additionally, we use microfluidic mono- and co-culture to demonstrate maintenance of reproductive organ function when microfluidically-coupled with pancreatic islets. To address the translational feasibility challenges associated with engineered microfluidic platforms, we developed a functioning fluidic culture prototype that is both cost-effective and compatible with common laboratory hardware. Through the development of this platform, we also identify and characterize the potential in vitro and in vivo toxicity induced due to exposure to 3D-printed “biocompatible” photopolymers, Dental SG and Dental LT. Together, this body of work demonstrates the utility of microphysiological systems in creating in vitro models in reproductive biology as well as the need for specific design considerations for these applications.
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