Controlling Strain Energy Density in 3D Cellular Collagen Constructs During Complex Loads

Mechanical stimulation applied to damaged soft tissues, such as ligament, can promote tissue remodeling to accelerate healing. To help identify treatments that encourage ligament healing, bioreactors have been designed to subject 3D cellularized constructs to various loading conditions in order to determine the mechanical mechanisms that trigger cell-mediated repair. An innovative approach is to use a bioreactor to apply controlled states of biaxial stress to study the effects of strain energy density and distortion energy on cell activity. Tissue distortion has been linked to changes in the structure and function of ligament, yet the specific impact of distortion energy on cell response has not been quantified. This is due to challenges in establishing a method to apply targeted levels of strain energy density to cellularized constructs. The goal of this study was to develop a novel methodology of subjecting 3D cellularized constructs to differing magnitudes of distortion energy while maintaining a targeted strain energy density. To vary the levels of distortion energy, the 3D cellular constructs were subjected to simple and complex loading conditions using a biaxial bioreactor. The bioreactor was able to accurately apply a targeted strain energy density of 300 J/m3 to the constructs during the various loading conditions with an average error of 12.7%. The complex loading conditions generated over 2-fold greater distortion energy than the simple loading conditions and was 22% greater when fibroblast cells were present. For the first time, this study has developed an experimental methodology to control the total strain energy density in a localized region of 3D cellular constructs as well as quantify the distortion energy in these constructs