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RESEARCH ARtiClE

Fabrication of biomimetic placental barrier structures

within a microfluidic device utilizing two-photon

polymerization

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Denise Mandt , Peter Gruber , Marica Markovic , Maximillian Tromayer , Mario Rothbauer ,
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Sebastian Rudi Adam Kratz , Syed Faheem Ali , Jasper Van Hoorick , Wolfgang Holnthoner ,
Severin Mühleder , Peter Dubruel , Sandra Van Vlierberghe , Peter Ertl , Robert Liska ,
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Aleksandr Ovsianikov 1,2*
1 Institute of Materials Science and Technology, TU Wien, Vienna Austria
2 Austrian Cluster for Tissue Regeneration, Austria
3 Institute of Applied Synthetic Chemistry, TU Wien, Vienna Austria
4 Polymer Chemistry and Biomaterials Group, Centre of Macromolecular Chemistry, Ghent University, Ghent, Belgium
5 Brussels Photonics, Department of Applied Physics and Photonics, Vrije Universiteit Brussel, Brussels, Belgium
6 Ludwig Boltzmann Institute of Experimental and Clinical Traumatology, Vienna, Austria
Abstract: The placenta is a transient organ, essential for development and survival of the unborn fetus. It interfaces the
body of the pregnant woman with the unborn child and secures transport of endogenous and exogenous substances. Maternal
and fetal blood are thereby separated at any time, by the so-called placental barrier. Current in vitro approaches fail to model
this multifaceted structure, therefore research in the field of placental biology is particularly challenging. The present study
aimed at establishing a novel model, simulating placental transport and its implications on development, in a versatile but
reproducible way. The basal membrane was replicated using a gelatin-based material, closely mimicking the composition
and properties of the natural extracellular matrix. The microstructure was produced by using a high-resolution 3D printing
method – the two-photon polymerization (2PP). In order to structure gelatin by 2PP, its primary amines and carboxylic
acids are modified with methacrylamides and methacrylates (GelMOD-AEMA), respectively. High-resolution structures
in the range of a few micrometers were produced within the intersection of a customized microfluidic device, separating
the x-shaped chamber into two isolated cell culture compartments. Human umbilical-vein endothelial cells (HUVEC)
seeded on one side of this membrane simulate the fetal compartment while human choriocarcinoma cells, isolated from
placental tissue (BeWo B30) mimic the maternal syncytium. This barrier model in combination with native flow profiles
can be used to mimic the microenvironment of the placenta, investigating different pharmaceutical, clinical and biological
scenarios. As proof-of-principle, this bioengineered placental barrier was used for the investigation of transcellular transport
processes. While high molecular weight substances did not permeate, smaller molecules in the size of glucose were able
to diffuse through the barrier in a time-depended manner. We envision to apply this bioengineered placental barrier for
pathophysiological research, where altered nutrient transport is associated with health risks for the fetus.

Keywords: high resolution 3D printing; placental barrier; model; microstructure; two-photon polymerization

*Correspondence to: Aleksandr Ovsianikov, Institute of Materials Science and Technology, TU Wien, Getreidemarkt 9, 1060 Vienna, Austria;
aleksandr.ovsianikov@tuwien.ac.at (ORCID: 0000-0001-5846-0198)

Received: May 14, 2018; Accepted: June 18, 2018; Published Online: July 3, 2018

Citation: Mandt D, Gruber P, Markovic M, 2018, Fabrication of biomimetic placental barrier structures within a
microfluidic device utilizing two-photon polymerization. Int J Bioprint, 4(2): 144. http://dx.doi.org/10.18063/IJB.v4i2.144

Fabrication of biomimetic placental barrier structures within a microfluidic device utilizing two-photon polymerization. © 2018 Mandt D, et al. This is an
Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 4.0 International License (http://creativecommons.
org/licenses/by-nc/4.0/), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
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