From Clinic to Computation: Multiscale Bioengineering Strategies for Durable Biological Aortic Valve Replacements

Bioprosthetic aortic valves, especially those implanted via transcatheter methods, have transformed the treatment of aortic stenosis. Nevertheless, their long‐term durability is still limited by structural valve deterioration. While clinical and hemodynamic factors have been extensively reviewed, the material science perspective on bioprosthetic valve deterioration has received comparatively less attention. Structural valve deterioration is, however, a complex, multiscale, and multifactorial process, in which mechanical fatigue and calcification of bovine or porcine pericardial tissue play central roles. For this reason, this review focuses on the pericardium itself—the engineered soft tissue at the core of bioprosthetic valves. The experimental techniques used to characterize its properties across multiple length scales, from molecular composition to macroscopic mechanics, are examined, highlighting how these multiscale measurements reveal critical structure–function relationships. Such insights are crucial for more accurate modeling of pericardial behavior and for understanding its deterioration in vivo. By integrating bioengineering, advanced physical characterization, and computational modeling, a framework is outlined that links material properties to valve‐level performance and, ultimately, clinical durability. This perspective not only advances the fundamental understanding of structural valve deterioration but also provides guidance for designing next‐generation bioprosthetic and synthetic polymeric valves with improved longevity.