Controlling placental spheroid growth and phenotype using engineered synthetic hydrogel matrices

Area of Science:

• Reproductive biology
• Biomaterials science
• Developmental biology

Background:

• Current in vitro human placental models are limited, failing to replicate the native microenvironment.
• Existing models include 2D cultures and poorly defined 3D hydrogels like Matrigel™, which lack environmental control and exhibit variability.
• Understanding human placental development requires more accurate in vitro models.

Purpose of the Study:

• To engineer a highly defined, synthetic hydrogel system for creating human placental spheroids.
• To evaluate the capacity of tunable synthetic hydrogels to support trophoblast viability, function, and phenotype.
• To compare the performance of synthetic hydrogels against standard Matrigel™ for placental spheroid culture.

Main Methods:

• Utilized a library of synthetic poly(ethylene glycol)-based hydrogels with tunable degradability.
• Incorporated placenta-derived extracellular matrix adhesive ligands into the hydrogel system.
• Cultured three human trophoblast cell lines in the hydrogels to form placental spheroids.
• Assessed spheroid viability, proliferation, function, and protein expression via proteomics and secretion assays.

Main Results:

• Degradable synthetic hydrogels significantly enhanced placental spheroid viability, proliferation, and function compared to Matrigel™.
• The synthetic hydrogel system provided precise control over the microenvironment for spheroid development.
• Proteomics and functional assays revealed that culture conditions modulate trophoblast cell phenotype.

Conclusions:

• Engineered synthetic hydrogels offer a superior platform for creating human placental spheroids in vitro.
• This advanced model provides precise control over the microenvironment, crucial for studying placental development.
• Improved in vitro models are essential for advancing the understanding of early human placental behavior and development.