Tissue-like Viscoelasticity Drives Muscle Stem Cell Expansion Through Mechanical Memory Formation

Muscle-like dual-network hydrogel viscoelasticity drives skeletal muscle stem cell expansion by creating a viscoelastic mechanical memory that stabilizes adhesions and Rac-Akt signaling.

• Why it matters: Rigid culture substrates linked to reduced regenerative potential in MuSCs likely involve elastic mechanical memory, but it was unknown whether tissue-like viscoelasticity can also encode persistent fate cues.
• What they did: Engineered dual-network hydrogels decoupled stiffness, stress relaxation, and adhesive ligand presentation to match native muscle viscoelastic properties, then assessed MuSC activation and expansion.
• The result: Physiological viscoelastic substrates promoted in vitro MuSC activation and accelerated expansion to match in vivo activation timescales, with focal adhesion stabilization and enhanced Rac-Akt signaling supporting progenitor expansion and persistent stem-like phenotype maintenance.

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