Mechanical overload decreases tenogenic differentiation compared to physiological load in bioartificial tendons

Area of Science:

• Biomaterials science
• Tissue engineering
• Mechanobiology

Background:

• Tenocytes, specialized fibroblasts, require mechanical load for tendon homeostasis.
• The impact of mechanical overload versus physiological load on tenogenic differentiation remains unclear.

Purpose of the Study:

• To investigate the effects of mechanical overload and physiological load on tenogenic differentiation in fibroblasts.
• To compare the cellular and molecular responses to different mechanical loading conditions in a 3D bioartificial tendon model.

Main Methods:

• Murine fibroblasts were cultured in 3D bioartificial tendons (BATs).
• BATs were subjected to uniaxial sinusoidal elongation at either overload (0-16%) or physiological (0-8%) load conditions for 7 days.
• Gene expression of tenogenic and extracellular matrix markers, along with protein levels of interleukin-6, were analyzed.

Main Results:

• Mechanical overload significantly decreased tenogenic and extracellular matrix gene expression compared to physiological load.
• Overload increased matrix metalloproteinase 3 (Mmp3) and interleukin-6 levels.
• Physiological load increased Mohawk homeobox (Mkx) and tenomodulin (Tnmd) expression compared to controls, suggesting beneficial effects.

Conclusions:

• Mechanical overload negatively impacts tenogenic differentiation and promotes inflammation and ECM remodeling in fibroblasts.
• Physiological mechanical load may induce beneficial effects on tenogenic differentiation and matrix production.
• These findings highlight the critical role of mechanical loading magnitude in regulating tendon cell behavior.