Drug transport across the human placenta: review of placenta-on-a-chip and previous approaches

Abstract

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.

Manufacturing of poly(ethylene glycol diacrylate)-based hollow microvessels using microfluidics

“…24,25 Under these ex vivo conditions, however, the preservation of real whole human blood and tissue can restrict the output of experimental results, and biases can arise during donor selection. [25][26][27] Fortunately, by recreating human microvessels in vitro, these in vivo and ex vivo barriers can be overcome. For instance, microuidic devices have been found to enable the precision control of dynamic-ow environments, endothelial cell culture, and physiological properties of an in vitro 3D microvasculature system for days on end.…”

“…For instance, microuidic devices have been found to enable the precision control of dynamic-ow environments, endothelial cell culture, and physiological properties of an in vitro 3D microvasculature system for days on end. [26][27][28][29][30][31][32][33][34][35] Examples of tissue-engineered microvessels can be found in the human lung, 36,37 heart, 38 kidneys 39 and blood-brain barrier, 40 and have been used to treat sickle-cell and thrombotic diseases. 41,42 In our microuidic device, though, we have set out to exclude the manual rolling of lms and complex cell-seeding procedures and produce a simple platform for generating hollow synthetic multiaxial microvessels.…”

Microphysiological Modeling of the Human Endometrium

“…72,78 Reproductive MPS are of particular interest because of their potential to recapitulate the complex hormonal feedback and feedforward signals between reproductive tissues and organs. 70,71 As a result, MPS of different reproductive organs, including the endometrium, [75][76][77] placenta, [79][80][81] oviduct, 82,83 amnion and fetal membrane, [84][85][86] as well as a multiorgan microfluidic framework of the female reproductive tract, 78 have been built.…”

Maternally administered naltrexone and its major active metabolite 6β-naltrexol transport across the placental barrierin vitro

“…10 The downside of using these models for testing is that while their anatomies resemble those of human anatomy, their placental tissues lack the analogous cellular and tissue interactions. 11 In addition to in vivo as a form of NTX testing, placebo-controlled testing has also been utilized to some extent. [12][13][14] For the most part, these studies have recorded only psychological, and antipruritic reactions from NTX and did not directly evaluate opioid exposure in the placental tissue.…”

“…[18][19][20][21] Microfluidic devices provide us with the ability to culture and manage cellular and subcellular environments within our microchip, maintain fixed compositions of our cell lines, and replicate fluid movement in parallel layers. 11,[22][23][24][25][26][27][28] Our microfluidic device (( Figure 1 (d)-(f-f)) was fabricated using standard lithography techniques. [29][30][31][32] To represent the human placenta's endothelium and trophoblastic epithelium, human umbilical vein endothelial cells (HUVECs) and trophoblasts cells (BeWo) were cultured accordingly.…”