Quantifying Distortion Energy in Collagen Matrices Subjected to Complex Loads Using a Biaxial Bioreactor

Mechanical loads, such as tension, compression, and shear, can stimulate growth and remodeling in musculoskeletal soft tissues. In order to test and validate theories that describe this mechanobiological response, bioreactors have been designed to apply various loading conditions to cellularized constructs during an in vitro culture period. Conventional bioreactors are limited to applying mechanical loads along one preferred axis, but biaxial bioreactors can simultaneous apply tensile and compressive loads, which mimic the physiological loading environment of connective tissue. A novel application of biaxial bioreactors is to apply controlled states of planar stress in order to study the effect of strain energy, which is the stored energy from deformation, on cellular behavior. Furthermore, strain energy can be decomposed into hydrostatic and distortion (deviatoric) energy, which is related to volume change and material distortion, respectively. Tissue distortion has been linked to changes in the structure and function of tendon and ligament, yet the specific impact of distortion energy on tissue remodeling has not been quantified due to challenges in applying targeted levels of strain energy to cellular constructs. Therefore, a need exists to develop an experimental methodology that can apply varying levels of distortion, while maintaining a constant strain energy density, to understand how distortion specifically influences the cellular activity, matrix structure, and mechanical function of cellularized constructs. By identifying the specific mechanical mechanisms that trigger cells to remodel and repair, scientists and physicians will be better able to treat and prevent connective tissue disorders.

The objective of this research is to validate a novel method of subjecting 3D collagen constructs to differing magnitudes of distortion energy while maintaining a targeted strain energy density. We hypothesize that combined loads will increase distortion energy relative to single tensile or compressive loads.