Engineered Full-Length Fibronectin-Hyaluronic Acid Hydrogels for Stem Cell Engineering

Area of Science:

• Biomaterials Science
• Cell Biology
• Tissue Engineering

Background:

• Mechanical cues regulate stem cell behavior, but current biomaterials often fail to mimic the complex extracellular matrix (ECM).
• Hyaluronic acid (HA) and fibronectin (FN) are key ECM components influencing cell fate.
• Precisely tuning substrate properties is crucial for understanding mechanobiology.

Purpose of the Study:

• To engineer advanced hydrogels that recapitulate ECM complexity for stem cell mechanobiology.
• To investigate the role of fibronectin (FN) concentration and hydrogel stiffness on stem cell behavior.
• To compare stem cell responses in 2D and 3D environments within these engineered hydrogels.

Main Methods:

• Covalently crosslinking full-length fibronectin (FN) to hyaluronic acid (HA) to create hydrogels.
• Independently controlling hydrogel mechanical properties and FN concentration.
• Culturing human mesenchymal stem cells (MSCs) on (2D) surfaces and encapsulated within (3D) hydrogels.

Main Results:

• Achieved control over hydrogel mechanics independent of FN concentration.
• Demonstrated successful culturing of viable cells both on and within the hydrogels.
• Observed increased nuclear translocation of yes-associated protein (YAP) with higher FN on 2D substrates, but not in 3D encapsulated cells.

Conclusions:

• Developed complex hydrogels that mimic ECM features for stem cell control.
• Highlighted distinct MSC responses to FN in 2D versus 3D environments.
• Provided a platform for studying stem cell mechanobiology in more biologically relevant settings.