A Non-Invasive Material Characterization Framework for Bioprosthetic Heart Valves MOSTAFA ABBASI, 1 MOHAMMED S. BARAKAT, 1 DANNY DVIR, 2 and ALI N. AZADANI 1 1 The DU Cardiovascular Biomechanics Laboratory, Department of Mechanical and Materials Engineering, University of Denver, Denver, CO, USA; and 2 Department of Medicine, Division of Cardiology, University of Washington, Seattle, WA, USA (Received 17 April 2018; accepted 11 September 2018) Associate Editor Arash Kheradvar oversaw the review of this article. Abstract—Computational modeling and simulation has become more common in design and development of bioprosthetic heart valves. To have a reliable computational model, considering accurate mechanical properties of bio- logical soft tissue is one of the most important steps. The goal of this study was to present a non-invasive material charac- terization framework to determine mechanical propertied of soft tissue employed in bioprosthetic heart valves. Using integrated experimental methods (i.e., digital image correla- tion measurements and hemodynamic testing in a pulse duplicator system) and numerical methods (i.e., finite element modeling and optimization), three-dimensional anisotropic mechanical properties of leaflets used in two commercially available transcatheter aortic valves (i.e., Edwards SAPIEN 3 and Medtronic CoreValve) were characterized and compared to that of a commonly used and well-examined surgical bioprosthesis (i.e., Carpentier-Edwards PERIMOUNT Mag- na aortic heart valve). The results of the simulations showed that the highest stress value during one cardiac cycle was at the peak of systole in the three bioprostheses. In addition, in the diastole, the peak of maximum in-plane principal stress was 0.98, 0.96, and 2.95 MPa for the PERIMOUNT Magna, CoreValve, and SAPIEN 3, respectively. Considering leaflet stress distributions, there might be a difference in the long- term durability of different TAV models. Keywords—Inverse finite element simulation, Bioprosthetic heart valves, Three-dimensional anisotropic mechanical properties, Optimization, Fung constitutive model, Holzap- fel–Gasser–Ogden constitutive model, Carpentier-Edwards PERIMOUNT Magna, Edwards SAPIEN 3, Medtronic CoreValve. INTRODUCTION Pre-clinical assessment and verification of life sus- taining implantable medical devices such as prosthetic heart valves are essential and required by regulatory agencies. As a result, in vitro bench-top and pre-clinical animal testing have been employed to verify safety and improve design features of prosthetic heart valves. 30 However, the pre-clinical studies are time-consuming and costly, and therefore, the tests may potentially inhibit exploration and use of novel materials and designs in prosthetic heart valves. In the past few years, computational modeling and simulation have been widely employed to expedite design and optimization of new medical devices. 20,43 Computational simula- tions can play a pivotal role in design and development of prosthetic heart valves by reducing the need to perform expensive pre-clinical tests. Furthermore, regulatory agencies such as the U.S. Food and Drug Administration (FDA) and EU Medical Device Reg- ulatory System currently accept validated computa- tional modeling and simulation as a scientific evidence in regulatory submissions. 18 In the past decade, use of bioprosthetic heart valves for aortic valve replacement has increased signifi- cantly. 39 The trend was due to promising improve- ments in the long-term durability of surgical aortic valves (SAVs) and the advent of transcatheter aortic valves (TAVs). 14,29 Randomized clinical trials proved transcatheter aortic valve replacement (TAVR) im- proved survival over medical therapy for inoperable patients with severe symptomatic aortic steno- sis. 33,38,41,45,46 Furthermore, transfemoral TAVR showed equivalent or superior outcomes when com- pared to surgical aortic valve replacement (SAVR) for the high-risk 5,35,40,56 and intermediate-risk 37,48 Address correspondence to Ali N. Azadani, The DU Cardio- vascular Biomechanics Laboratory, Department of Mechanical and Materials Engineering, University of Denver, Denver, CO, USA. Electronic mail: Ali.Azadani@du.edu Annals of Biomedical Engineering (Ó 2018) https://doi.org/10.1007/s10439-018-02129-5 Ó 2018 Biomedical Engineering Society