In Silico Performance of a Recellularized Tissue-Engineered Transcatheter Aortic Valve

Abstract

Commercially available heart valves have many limitations, such as a lack of remodeling, risk of calcification, and thromboembolic problems. Many state-of-the-art tissue-engineered heart valves (TEHV) rely on recellularization to allow remodeling and transition to mechanical behavior of native tissues. Current in vitro testing is insufficient in characterizing a soon-to-be living valve due to this change in mechanical response; thus, it is imperative to understand the performance of an in situ valve. However, due to the complex in vivo environment, this is difficult to accomplish. Finite element (FE) analysis has become a standard tool for modeling mechanical behavior of heart valves; yet, research to date has mostly focused on commercial valves. The purpose of this study has been to evaluate the mechanical behavior of a TEHV material before and after 6 months of implantation in a rat subdermis model. This model allows the recellularization and remodeling potential of the material to be assessed via a simple and inexpensive means prior to more complex ovine orthotropic studies. Biaxial testing was utilized to evaluate the mechanical properties, and subsequently, constitutive model parameters were fit to the data to allow mechanical performance to be evaluated via FE analysis of a full cardiac cycle. Maximum principal stresses and strains from the leaflets and commissures were then analyzed. The results of this study demonstrate that the explanted tissues had reduced mechanical strength compared to the implants but were similar to the native tissues. For the FE models, this trend was continued with similar mechanical behavior in explant and native tissue groups and less compliant behavior in implant tissues. Histology demonstrated recellularization and remodeling although remodeled collagen had no clear directionality. In conclusion, we observed successful recellularization and remodeling of the tissue giving confidence to our TEHV material; however, the mechanical response indicates the additional remodeling would likely occur in the aortic/pulmonary position.

Heart Valve Biomechanics: The Frontiers of Modeling Modalities and the Expansive Capabilities of Ex Vivo Heart Simulation

“…The study of prosthetic valvular replacements, particularly of the AV, is another area where in silico models are making great strides. Using computational flow or imaging-based models, researchers have created unique metrics that evaluate valvular replacement performance, addressing aspects such as leaflet thrombosis, abnormal flow patterns, blood damage, hinge design outcomes, paravalvular leakage, and left ventricular dynamics, while also creating novel preoperative, patient-specific planning protocols and prediction tools for surgical or transcatheter interventions ( 22 – 32 ). These models provide detailed views through unique quantifications, developing deeper intuition behind the valvular mechanics.…”

Rate-dependent mechanical behaviour of semilunar valves under biaxial deformation: From quasi-static to physiological loading rates

“…In the arena of semilunar heart valves, in specific, our results may also provide a comprehensive benchmark for comparing the mechanical behaviour of tissue-engineered versus native valves. A recent study on modelling the behaviour of tissueengineered AVs employs a rate of 0.02 s -1 (Noble et al 2019), citing preceding studies using the same range of rates. In view of the current study, the documented mechanical behaviour at 0.02 s -1 may not be directly representative of the in vivo behaviour.…”