Collagen Scaffold Viscoelasticity Regulates Muscle Cell Phenotype

Area of Science:

• Biomaterials Science
• Tissue Engineering
• Regenerative Medicine

Background:

• Current biomaterials fail to fully restore skeletal muscle function post-injury, leading to permanent loss.
• Growing evidence highlights the importance of matrix viscoelasticity in regenerative processes.
• Understanding how mechanical properties influence cell behavior is key for effective muscle repair strategies.

Purpose of the Study:

• To investigate the hypothesis that matrix viscoelasticity regulates muscle cell function and regeneration.
• To explore the impact of different hydrogel viscoelastic properties on myoblast and satellite cell behavior.
• To develop advanced biomaterials that can guide specific cellular responses for skeletal muscle recovery.

Main Methods:

• Utilized norbornene-modified type I collagen hydrogels crosslinked with a tetrazine-based system.
• Engineered hydrogels with varying viscoelastic properties, specifically slow-relaxing and fast-relaxing matrices.
• Assessed myoblast spreading, proliferation, differentiation, and satellite cell stemness on these engineered substrates.

Main Results:

• Myoblast spreading, proliferation, and differentiation were enhanced on and within slow-relaxing hydrogels.
• Satellite cell stemness, vital for muscle regeneration, was maintained exclusively on soft, fast-relaxing hydrogels.
• Demonstrated a direct correlation between collagen-based substrate viscoelasticity and muscle cell phenotype in vitro.

Conclusions:

• Hydrogel viscoelasticity directly influences skeletal muscle cell behavior, including proliferation, differentiation, and stemness.
• Tailoring matrix mechanical properties, specifically relaxation time and stiffness, is critical for optimizing muscle regeneration.
• These findings provide a foundation for designing advanced biomaterials to guide cellular functions essential for skeletal muscle repair.