Hydrogels for 3D Neural Tissue Models: Understanding Cell-Material Interactions at a Molecular Level

Area of Science:

• Biomaterials Science
• Neuroscience
• Tissue Engineering

Background:

• Developing 3D neural tissue analogs is crucial for neural interfaces, neurodegenerative disease treatments, and in vitro cell-material interaction studies.
• Current synthetic hydrogels struggle to support complex neural network development, often requiring biologically derived constructs for long-term success.

Purpose of the Study:

• To investigate the interplay between cell-cell communication and cell-material interactions in a poly (vinyl alcohol) functionalized with gelatin and sericin (PVA-SG) hydrogel.
• To probe short-term interactions influencing neural network growth and the development of a functional neural model.
• To understand the limitations of PVA-SG hydrogels in supporting neural network development by examining astrocyte behavior.

Main Methods:

• Encapsulation of primary ventral mesencephalic (VM) neural cells in PVA-SG hydrogels.
• Examination of molecular cues related to mechanosensory interaction and cell cycle.
• Quantification of neuronal and astrocyte populations, neural process outgrowth, and MMP-2 production.

Main Results:

• Neuronal presence remained constant, but the astrocyte population decreased over 10 days.
• Neural process outgrowth significantly reduced due to lack of astrocytic support.
• PVA-SG hydrogels limited astrocyte actin polymerization and YAP translocation, leading to cell cycle arrest (indicated by p27^/ gene upregulation) and negligible MMP-2 production compared to 2D controls.

Conclusions:

• Astrocyte-material interactions are critical for neural network development in 3D hydrogels.
• The spatial constraints of PVA-SG hydrogels impede astrocyte function, negatively impacting neural growth.
• Future hydrogel designs must incorporate mechanisms for cell-mediated remodeling to accommodate cell migration and neural process extension.