Dynamic Biaxial Loading of Cell-Seeded Tissue Equivalents

October 10, 2024

Motivation

Smooth muscle cells (SMCs) are essential in maintaining proper function of the aorta and are constantly subjected to dynamic multiaxial loading of various magnitudes. For example, loads can temporarily increase during exercise or permanently during disease, such as hypertension. However, only a few quantitative studies report the forces the SMCs establish and maintain in collagen-based tissue equivalents under dynamic biaxial loading.

Picture showing the possible boundary conditions for cell-seeded tissue equivalents.

Methods

To begin to close this gap, we use the previously developed biaxial bioreactor to subject collagen gels seeded with aortic SMCs to different biaxial loading conditions. First, the effects of increased biaxial loads were examined using cyclic equibiaxial loading of different amplitudes (5% (E5) vs. 10% (E10) strain). Second, the effects of cyclic equibiaxial versus cyclic strip-biaxial loading were examined while keeping the amplitude of the stretching the same (E5 vs. S5-cyclic vs. S5-static). Note that a strip biaxial test holds the sample at a constant overall stretch along one axis (S5-static) while cyclically stretching in the orthogonal axis (S5-cyclic), which resembles mechanical constraints experienced by SMCs over a cardiac cycle in the aorta.

Picture showing the ratio of mean forces during cyclic loading to homeostatic forces before cyclic loading.

Results

Irrespective of loading amplitude and boundary condition, similar mean steady-state forces emerged across all tests. Additionally, the stiffness-force relationships – the stiffness at a given force – of the gels were remarkably similar. Taken together, this suggests that vascular SMCs mechano-adapt to maintain a preferred force or stress.