Modeling and simulating time-dependent changes in soft-tissue derived bioprosthetic heart valve biomaterial in response to cyclic loading

Soft tissue-derived exogenously cross-linked (EXL) biomaterials continue to be the best choice for the fabrication of bioprosthetic heart valves (BHV). Despite years of use, our understanding of these biomaterials and of the mechanisms leading to their failure remain at an empirical level. The need for advancements in modeling their behavior is further underscored by the development of percutaneously-delivered BHV devices. While these devices offer reduced surgical risk, they also present additional challenges for the design of the leaflets due to limitations in thickness and folding during delivery, resulting in a 2-year mortality rate of 33.9% in general. Thus, we seek to develop a framework for modeling and simulating soft-tissue-derived EXL biomaterials, accounting for the effects of exogenous cross-linking in permanent set and mechanical fatigue. Such approaches can significantly improve the accuracy and reliability of long-term predictions of durability and mechanical function. Firstly, we will establish the form of a nonlinear hyperelastic meso-scale structural constitutive model (MSSCM) for fibrous soft tissues, that can accurately capture the mechanical response of common soft tissues used as a basis for EXL biomaterial. Secondly, we will study the effect of exogenous crosslinks on these tissues using glutaraldehyde (GLUT) EXL bovine pericardium. GLUT-EXLs form polymeric chains through the cross-linking process which more tightly bonds the fibers to the matrix, increasing the non-fibrous matrix stiffness and fiber-fiber interactions. However, GLUT EXLs undergo Schiff-base reactions that lead to scission-healing behaviors that change the geometry of BHVs. We model this effect based on first-order kinetics of the scission healing reaction and validate it using static strain, cyclic strain, and stress control experiments. Next, we will develop a full 3D finite element implementation of the MSSCM with the modifications for EXL for real device applications. We then parametrically examine the changes in geometry and stress distribution of BHVs overtime, exploring initial geometries and material properties which may minimize the risks of the former effects. With this, we aim to develop a better understanding of the underlying process that occurs during long-term cyclic loading through our constitutive modeling approach and device level applications and translate the insights gained to improve BHV design and durability.Biomedical Engineerin