Tensile Loaded Tissue-Engineered Human Tendon Constructs Stimulate Myotube Formation.

Area of Science:

• Biomedical Engineering
• Cell Biology
• Musculoskeletal Research

Background:

• Skeletal muscle regeneration relies on muscle stem cells and interstitial cells.
• Tendon tissue, like muscle, adapts to mechanical loading.
• The interaction between skeletal muscle and adjacent tendon during regeneration is not well understood.

Purpose of the Study:

• To investigate if factors from mechanically loaded human tendon constructs stimulate myogenic cell proliferation and differentiation.
• To explore the signaling crosstalk between tendon and muscle tissues in response to mechanical stimuli.

Main Methods:

• Engineered human tendon constructs were subjected to uniaxial tensile loading (4% strain at 0.5 Hz for 4 hours).
• Conditioned media from loaded and control tendon constructs were applied to human-derived myogenic cells (myoblasts).
• Immunofluorescence and gene expression analyses were used to assess myoblast proliferation, differentiation, and fusion.

Main Results:

• Conditioned media from mechanically loaded tendon constructs increased myotube fusion index and diameter.
• Key genes (Myostatin, myosin heavy chain 7, AXIN2) were downregulated in myotubes treated with loaded tendon media.
• No significant difference in myoblast proliferative potential (Ki67+, BrdU+) was observed between groups.

Conclusions:

• Tendon fibroblasts release factors upon mechanical loading that enhance myotube formation, indicating improved muscle regeneration.
• Mechanical loading influences signaling between skeletal muscle and tendon, crucial for musculoskeletal tissue development and repair.
• This study highlights the importance of the muscle-tendon unit's integrated response to mechanical loading for human musculoskeletal health.