Distortion Energy Drives Cellular and Mechanical Changes in Fibroblast-Seeded Collagen Scaffolds Under Cyclic...

Area of Science:

• Biomaterials Science
• Cellular Mechanobiology
• Tissue Engineering

Background:

• Fibroblast activity in soft tissues is governed by the mechanical properties of the extracellular matrix.
• Previous models using stress or strain invariants struggle to predict cell responses across different loading configurations.
• A unifying theory for fibroblast-mediated matrix remodeling is needed.

Purpose of the Study:

• To investigate distortion energy as a predictor of fibroblast cellular and mechanical responses.
• To compare distortion energy with traditional stress and strain invariants across multiple loading conditions.
• To determine if distortion energy can unify predictions of cell response across diverse mechanical environments.

Main Methods:

• Murine fibroblasts were seeded onto collagen scaffolds and subjected to cyclic uniaxial tension, uniaxial compression, or biaxial tension-compression for 7 days.
• A multiaxial bioreactor applied approximately 40 J/m3 of strain energy across all loading types.
• Mechanical properties, cell density, and fiber alignment were quantified before and after stimulation.

Main Results:

• Changes in cell density showed the strongest correlation with distortion energy (partial r=0.85, p=0.001) compared to stress/strain invariants.
• Distortion energy positively correlated with tensile stiffness but not compressive properties.
• Distortion energy proved to be the superior predictor of cellular and mechanical changes across varied loading scenarios.

Conclusions:

• Distortion energy is a robust predictor of fibroblast-mediated matrix remodeling across diverse mechanical loads.
• This scalar measure offers a unifying framework for understanding cell behavior in response to mechanical stimuli.
• Distortion energy may represent a fundamental physical driver of fibroblast activity and extracellular matrix remodeling.