Stress relaxation timescale and hydrogel network connectivity regulate neural progenitor cell stemness and...

Area of Science:

• Biomaterials Science
• Stem Cell Biology
• Tissue Engineering

Background:

• Neural progenitor cells (NPCs) are crucial for cell replacement therapies.
• Maintaining NPC stemness and expansion in 3D biomaterials is challenging.

Purpose of the Study:

• To investigate how hydrogel properties influence NPC phenotype in 3D culture.
• To identify key design parameters for optimizing NPC expansion and stemness maintenance.

Main Methods:

• Fabrication of tunable 3D hydrogels with varying stress relaxation and network connectivity.
• Culturing NPCs within these hydrogels and assessing stemness markers, proliferation, and differentiation capacity.
• Analyzing the role of integrin-cell and cadherin-cell interactions.

Main Results:

• Rapidly relaxing, low-connectivity hydrogels promoted NPC expansion as distributed single-cell networks, preserving stemness and differentiation potential.
• Slowly relaxing hydrogels or those lacking integrin-binding ligands led to NPC clustering, impaired proliferation, and reduced differentiation.
• Cadherin-mediated cell-cell contacts enhanced stemness maintenance, particularly in rapidly relaxing, low-connectivity networks.

Conclusions:

• Hydrogel stress relaxation timescale, network connectivity, and adhesive ligand presentation are critical for controlling NPC behavior in 3D.
• Optimized hydrogel design can support NPC stemness, expansion, and differentiation for therapeutic applications.