Issue 4, 2024

Controlling placental spheroid growth and phenotype using engineered synthetic hydrogel matrices

Abstract

The human placenta is a complex organ comprised of multiple trophoblast subtypes, and inadequate models to study the human placenta in vitro limit the current understanding of human placental behavior and development. Common in vitro placental models rely on two-dimensional culture of cell lines and primary cells, which do not replicate the native tissue microenvironment, or poorly defined three-dimensional hydrogel matrices such as Matrigelâ„¢ that provide limited environmental control and suffer from high batch-to-batch variability. Here, we employ a highly defined, synthetic poly(ethylene glycol)-based hydrogel system with tunable degradability and presentation of extracellular matrix-derived adhesive ligands native to the placenta microenvironment to generate placental spheroids. We evaluate the capacity of a hydrogel library to support the viability, function, and phenotypic protein expression of three human trophoblast cell lines modeling varied trophoblast phenotypes and find that degradable synthetic hydrogels support the greatest degree of placental spheroid viability, proliferation, and function relative to standard Matrigel controls. Finally, we show that trophoblast culture conditions modulate cell functional phenotype as measured by proteomics analysis and functional secretion assays. Engineering precise control of placental spheroid development in vitro may provide an important new tool for the study of early placental behavior and development.

Graphical abstract: Controlling placental spheroid growth and phenotype using engineered synthetic hydrogel matrices

Supplementary files

Article information

Article type
Paper
Submitted
25 Aug 2023
Accepted
29 Dec 2023
First published
03 Jan 2024

Biomater. Sci., 2024,12, 933-948

Controlling placental spheroid growth and phenotype using engineered synthetic hydrogel matrices

E. M. Slaby, S. B. Plaisier, S. R. Brady, S. C. Hiremath and J. D. Weaver, Biomater. Sci., 2024, 12, 933 DOI: 10.1039/D3BM01393F

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