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Fabrication of biomimetic placental barrier structures within a microfluidic device utilizing two-photon polymerization

           was investigated. The cultivation of HUVECs in co-  structures.
           culture media showed increased proliferation after 24   Another advantage of this model lies in the adapt-
           and 48 hours, compared to the control. This justifies   ability of the geometry. The in vitro model has to reflect
           the conclusion that serum concentrations slightly above   changes in surface area of the placenta, occurring during
                                                                                   [3]
           those in EGM-2 seem to enhance cell proliferation but   the course of pregnancy . The use of the 2PP technique
           does not negatively influence cell viability [37] . First   using  CAD models allows precise structural adaptability
           tests with the established placenta-on-a-chip model   of the certain geometry depending on the investigated
           have shown that cell attachment and the formation of   stage of pregnancy. To this end, surface area can be
           a confluent cell layer on the walls of GelMOD-AEMA   increased or reduced by addition or removal of villous
           constructs was feasible. Both cells types, HUVEC and   loops, respectively.
           BeWo B30, were successfully seeded and cultured on   Conflicts of Interest
           the membrane walls for 7 days. Our future studies will
           include optimization of cell seeding conditions and   There are no conflicts to declare.
           investigation of active glucose transport through the
           membrane.                                           Acknowledgements
           5. Conclusions                                      The financial support by the FWO Flanders (FWO SB
                                                               PhD grant, J.V.H.), the Austrian Science Funds (FWF
           In conclusion, 2PP is an enabling manufacturing     Project No. I2444-N28, A.O.) as well as the European
           technology for establishing a versatile biomimetic on-  Union’s Horizon 2020 research and innovation program
           chip barrier structure suitable for the cultivation of   (grant agreement No. 685817) and European Research
           two different cell populations. In this work, collagen   Council (Starting Grant-307701, A.O.) is gratefully
           derived biopolymers, which resemble the extracellular   acknowledged. Furthermore, we thank the team of the
           matrix were applied instead of inorganic polymers.   material science and technology department as well as
           The compatibility of the microfabricated device with   our colleagues from the institute of applied synthetic
           microfluidic pumps enables its maintenance under    chemistry at the Technical University of Vienna, for their
           constant flow and thus the simulation of in vivo body   support and critical comments that greatly improved
           fluid  flow.  Customized  chip  design  and  channel   this work. The authors thank Dr. Tina Buerki-Thurnherr
           orientation thereby guarantee the tight separation of   (EMPA, Switzerland) for providing BeWo B30 cells.
           the culture compartments, with the advantage that the
           respective cell type stays in the intended compartment   References
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