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Bioprinting is an emerging and promising technique for fabricating 3D cell-laden constructs for various biomedical applications. In this paper, we employed 3D bioprinted GelMA-based models to investigate the trophoblast cell invasion phenomenon, enabling studies of key placental functions. Initially, a set of optimized material and process parameters including GelMA concentration, UV crosslinking time and printing configuration were identified by systematic, parametric study. Following this, a multiple-ring model (2D multi-ring model) was tested with the HTR-8/SVneo trophoblast cell line to measure cell movement under the influence of EGF (chemoattractant) gradients. In the multi-ring model, the cell front used as a cell invasion indicator moves at a rate of 85 ± 33 µm/day with an EGF gradient of 16 µM. However, the rate was dramatically reduced to 13 ± 5 µm/day, when the multi-ring model was covered with a GelMA layer to constrain cells within the 3D environment (3D multi-ring model). Due to the geometric and the functional limitations of multi-ring model, a multi-strip model (2D multi-strip model) was developed to investigate cell movement in the presence and absence of the EGF chemoattractant. The results show that in the absence of an overlying cell-free layer of GelMA, movement of the cell front shows no significant differences between control and EGF-stimulated rates, due to the combination of migration and proliferation at high cell density (6 × 10 6  cells/ml) near the GelMA surface. When the model was covered by a layer of GelMA (3D multi-strip model) and migration was excluded, EGF-stimulated cells showed an invasion rate of 21 ± 3 µm/day compared to the rate for unstimulated cells, of 5 ± 4 µm/day. The novel features described in this report advance the use of the 3D bioprinted placental model as a practical tool for not only measurement of trophoblast invasion but also the interaction of invading cells with other tissue elements.

3D Bioprinted GelMA Based Models for the Study of Trophoblast Cell Invasion