Due to the particular structure and functionality of the placenta, most current human placenta drug testing methods are limited to animal models, conventional cell testing, and cohort/controlled testing. Previous studies have produced inconsistent results due to physiological differences between humans and animals and limited availability of human and/or animal models for controlled testing. To overcome these challenges, a placenta‐on‐a‐chip system is developed for studying the exchange of substances to and from the placenta. Caffeine transport across the placental barrier is studied because caffeine is a xenobiotic widely consumed on a daily basis. Since a fetus does not carry the enzymes that inactivate caffeine, when it crosses a placental barrier, high caffeine intake may harm the fetus, so it is important to quantify the rate of caffeine transport across the placenta. In this study, a caffeine concentration of 0.25 mg mL −1 is introduced into the maternal channel, and the resulting changes are observed over a span of 7.5 h. A steady caffeine concentration of 0.1513 mg mL −1 is reached on the maternal side after 6.5 h, and a 0.0033 mg mL −1 concentration on the fetal side is achieved after 5 h.

One contribution of 15 to a theme issue 'Bioengineering in women's health, volume 2: pregnancy-from implantation to parturition'.In the past few decades, the placenta became a very controversial topic that has had many researchers and pharmacists discussing the significance of the effects of pharmaceutical drug intake and how it is a possible leading cause towards birth defects. The creation of an in vitro microengineered model of the placenta can be used to replicate the interactions between the mother and fetus, specifically pharmaceutical drug intake reactions. As the field of nanotechnology significantly continues growing, nanotechnology will become more apparent in the study of medicine and other scientific disciplines, specifically microengineering applications. This review is based on past and current research that compares the feasibility and testing of the placenta-on-a-chip microengineered model to the previous and underdeveloped in vivo and ex vivo approaches. The testing of the practicality and effectiveness of the in vitro, in vivo and ex vivo models requires the experimentation of prominent pharmaceutical drugs that most mothers consume during pregnancy. In this case, these drugs need to be studied and tested more often. However, there are challenges associated with the in vitro, in vivo and ex vivo processes when developing a practical placental model, which are discussed in further detail.

To understand the transport of pharmaceutical agents and their effects on developing fetus, we have created a placental microsystem that mimics structural phenotypes and physiological characteristic of a placental barrier. We have shown the formation of a continuous network of epithelial adherens junctions and endothelial cell–cell junctions confirming the integrity of the placental barrier. More importantly, the formation of elongated microvilli under dynamic flow condition is demonstrated. Fluid shear stress acts as a mechanical cue triggering the microvilli formation. Pharmaceutical agents were administered to the maternal channel, and the concentration of pharmaceutical agents in fetal channel for coculture and control models were evaluated. In fetal channel, the coculture model exhibited about 2.5 and 2.2% of the maternal initial concentration for naltrexone and 6β-naltrexol, respectively. In acellular model, fetal channel showed about 10.5 and 10.3% of the maternal initial concentration for naltrexone and 6β-naltrexol, respectively. Gene expressions of epithelial cells after direct administration of naltrexone and 6β-naltrexol to the maternal channel and endothelial cells after exposure due to transport through placental barrier are also reported.

While 3D cell cultures continue to grow in complexity and physiological relevance, more work must be done to reach the full potential of a real-time cell sensing system that is able to match the macro-and microenvironments of target tissues. 1D and 2D real-time sensors have been reliably created utilizing micro-and nano-electrodes, or planar electrodes, respectively. [1] This work furthers the cause by using biocompatible, graphene-laden microfibers as cellular constructs, which can be used in conjunction with 3D micro-electrode arrays for a highly complex real-time sensing system to analyze electrical cellto-cell communication that occurs within the brain. Additionally, this study works toward the important task of identifying genetic changes caused by manufacturing, and contrasting this against the effects of long-term encapsulation in four genes that are important to neural health, such as, tyrosine hydroxylase (TH), tubulin beta 3 class 3 (TUBB-3), interleukin 1 beta (IL-1β), and tumor necrosis factor alfa (TNF-α). Identifying the effects of manufacturing has been neglected in previous works, [2] and thus the current work provides a crucial understanding of the implications of using 3D cell cultures for tissue modeling.Hydrogels, with their high water content and the ease of diffusion across their borders, are ideal candidates for applications wherein the spatiotemporal properties of the cells must be controlled for long-term observation. [3] In particular, microfibers are well-suited for this purpose, as their higher surface-to-volume ratio expedites the diffusion of nutrients and waste across the cell border, while allowing for highly complex and specific scaffold geometries. [4,2,3b,3e,5] Cell-laden microfibers can be created in a number of different ways, including wetspinning/extrusion; [6] however, microfluidics provides unmatched control over the size, shape, and degredation rates of the resulting microfibers, while still allowing for all potential cell-safe gelation methods. [4,3h,7] In this way, a cell suspension might be mixed with a prepolymer solution before polymerization or gelation, thereby resulting in Engineering conductive 3D cell scaffoldings offer advantages toward the creation of physiologically relevant platforms with integrated real-time sensing capabilities. Dopaminergic neural cells are encapsulated into graphene-laden alginate microfibers using a microfluidic approach, which is unmatched for creating highly-tunable microfibers. Incorporating graphene increases the conductivity of the alginate microfibers by 148%, creating a similar conductivity to native brain tissue. The cell encapsulation procedure has an efficiency of 50%, and of those cells, ≈30% remain for the entire 6-day observation period. To understand how the microfluidic encapsulation affects cell genetics, tyrosine hydroxylase, tubulin beta 3 class 3, interleukin 1 beta, and tumor necrosis factor alfa are analyzed primarily with real-time reverse transcription-quantitative polymerase chain reaction and secondarily wi...

Striving for sustainable drug discovery, we have presented a proof-of-concept for studying the effects of pharmaceutical agents transported across the placental barrier on neural cells. The potential effects of pharmaceutical agents on fetus have made concerns about their use and require more studies to address these concerns. A placenta-on-a-chip model was fabricated and tested for transport of naltrexone (NTX) and its primary metabolite 6[Formula: see text]-naltrexol. The NTX/6[Formula: see text]-naltrexol transported from the maternal channel to the fetal channel was then collected from the fetal channel. To evaluate the behavior of neural cells following exposure to NTX and 6[Formula: see text]-naltrexol, perfusate from the fetal channel was directed toward the cultured N27 neural cells. Neural cells exposed to the transported NTX/6[Formula: see text]-naltrexol were then evaluated for gene expression and cell viability. Results showed significantly higher fold changes in IL-6 and TNF-[Formula: see text] expression when exposed to NTX/6[Formula: see text]-naltrexol. However, a lower fold change in IL-1[Formula: see text] expression was observed, while it remained the same in sphingosine kinase (sphk)1. Also, cell viability with NTX/6[Formula: see text]-naltrexol exposure was determined to be significantly lower ([Formula: see text]). This study has the potential to reveal the impact of pharmaceutical agents on the developing neural system of fetuses and their premature brains.