Effects of Enzyme-Based Removal of Collagen and Elastin Constituents on the Biaxial Mechanical Responses of Porcine Atrioventricular Heart Valve Anterior Leaflets

The leaflets of the atrioventricular heart valves (AHVs) regulate the one-directional flow of blood through a subtle coordination of the tissue's extracellular matrix (ECM) components, including collagen fibers, elastin fibers, and glycosaminoglycans. Dysfunction of the AHVs, such as those caused by unfavorable microstructural remodeling, results in valvular heart diseases and improper blood flow that can eventually lead to heart failure. To better understand mechanics and remodeling of the AHV leaflets and how therapeutics may inadvertantly cause adverse microstructural changes, a systematic characterization of the role of each ECM constituent in the biomechanical properties is warranted. Previous studies have quantified the contributions of the microstructural components to the tissue-level behavior for the semilunar valve leaflets, but not for the AHV leaflets. In this study, for the first time, we quantify the AHV leaflet microstructure-mechanics relationships, by using a three-step experimental procedure: (i) biaxial tensile and stress relaxation testing of the control (untreated) porcine AHV anterior leaflet specimens; (ii) enzyme treatment for removing a portion of either the collagen or elastin constituent; (iii) biaxial tensile and stress relaxation testing of the constituent-removed (treated) specimens. We observed that removing about 25-50% collagen from the leaflets resulted in a ~3% increase in the extensibility of the tissue and a ~50% increase in the stress relaxation behavior. Meanwhile, the removal of approximately 90-99% elastin led to a ~10% decrease in the extensibility of the leaflets and a ~75% increase in the stress relaxation behavior. These findings provide insight into the microstructure-mechanics relationship of the AHVs, and will be beneficial in the future developments and refinements of microstructurally informed constitutive models to simulate diseased and surgically-intervened AHV function.