Engineering hydrogels with homogeneous mechanical properties for controlling stem cell lineage specification.

Area of Science:

• Biomaterials science
• Cell biology
• Tissue engineering

Background:

• The extracellular matrix (ECM) exhibits inherent mechanical inhomogeneity due to its complex composition and nanoscale structure.
• Pathological conditions can exacerbate ECM mechanical inhomogeneity, impacting cellular behavior.
• Current synthetic hydrogels often overlook the critical role of mechanical homogeneity, limiting their biomimicry.

Purpose of the Study:

• To develop a method for controlling the mechanical homogeneity of poly(ethylene glycol) (PEG) hydrogels.
• To investigate the impact of hydrogel mechanical homogeneity on human embryonic stem cell (hESC) fate (differentiation vs. stemness).

Main Methods:

• Utilized host-guest chemistry to precisely control cross-linking in maleimide-thiol cross-linked PEG hydrogels.
• Engineered hydrogels with varying degrees of mechanical homogeneity.
• Assessed hESC responses, including actin assembly, YAP activation, and stemness maintenance.

Main Results:

• Demonstrated a method to tune hydrogel mechanical homogeneity using host-guest chemistry.
• Showed that inhomogeneous hydrogels disrupt actin assembly and reduce YAP activation in hESCs.
• Revealed that homogeneous hydrogels promote mechanotransduction, supporting stemness maintenance or directed differentiation.

Conclusions:

• Mechanical homogeneity of synthetic hydrogels is a critical factor influencing stem cell behavior and mechanotransduction.
• The developed method for creating homogeneous hydrogels offers a valuable tool for cell culture and tissue engineering.
• Controlling hydrogel homogeneity can guide stem cell fate, with broad implications for regenerative medicine.