Transcatheter aortic valve replacement (TAVR) has been proven to be the best course of treatment[1]. Since Cribier et al. completed the first TAVR in 2002, the field has undergone remarkable advancements. Even in patients with low surgical risk, recent data have demonstrated the non-inferiority and superiority of TAVR over surgical aortic valve replacement (SAVR)[2,3]. Currently, the most frequently used biological heart valves (BHVs) are those derived from the bovine pericardium, which are generally subjected to decellularization and glutaraldehyde cross-linking to ensure that the leaflets have low immunogenicity and other necessary properties (such as mechanical strength). However, bioprosthetic valves prepared from such materials are at risk of structural valve failure (SVD) after implantation in vivo, which is mainly manifested by calcification, fibrosis, rupture, and perforation of the leaflets. Calcification is the most important cause of SVD, thus limiting the useful life of the valve (usually no more than 15 years)[4]. In addition, the bovine pericardium suffers from the following problems: complicated pretreatment process, over-high and uneven thickness of the material, and the presence of α-Gal antigen and Ne5Gc antigen[5]. Because free aldehyde groups that arise during glutaraldehyde fixation are deactivated by anti-calcification treatment regimens and decades of design optimization, current commercially available BHVs have a significantly longer service life. However, these anti-calcification treatment strategies have only a small potential and have reached a bottleneck.

The fish swim bladder (FSB) is a sac-like organ between the digestive tract and spine in bony fish, and its main components are collagen, elastin, and glycosaminoglycans, with functions such as controlling elevation and assisting respiration. Compared to bovine pericardium, FSB has advantages, such as a wide range of sources, no risk of zoonotic virus transmission, and religious restrictions [6]. Our previous study showed that the FSB of Hypophthalmichthys molitrix has better biocompatibility, hemocompatibility, and calcification resistance than that of bovine pericardium[6]. Our group verified that the FSB of Hypophthalmichthys molitrix has immunogenic safety, indicating that it has a safe clinical application prospect[7]. FSB has been used to promote wound healing and as a substitute for dura mater[8], vascular patches [9,10], and pulmonary bioprosthetic valves [11]. Bai et al. used decellularized crucian carp FSBs loaded with rapamycin to prepare patches that inhibited intimal hyperplasia in both aortic and lower extremity venous vascular plaque rat models [10]. This team subsequently prepared decellularized crucian carp FSB patches loaded with mesenchymal stem cells, which were implanted into a rat aortic plaque model for 14 days and effectively inhibited intimal hyperplasia[9]. Xu et al. verified that FSB valves had good anti-calcification and hemodynamic properties using a sheep pulmonary valve replacement model[11]. However, no study has reported the application of fish bladder material in interventional aortic valves.

In this study, we report for the first time the in vitro long-term durability and in vivo potential of an FSB TAVR device. TAVR is subject to compression to ensure stable anchorage of self-expanding valves and avoid perivalvular leakage, and the latest Guidelines for Review of Registrations of Transcatheter Aortic Valve Systems in China also mention that the impact of fixture and release size on valve durability should be considered; thus, we utilized pulsatile flow testing, accelerated fatigue testing, and finite element methods to analyze the effects of compression on the hemodynamics, durability, and stress distribution of the FSB TAVR device to better study its functionality and durability after implantation. Finally, we implanted the FSB TAVR device in a domestic porcine model to verify the feasibility of using the FSB valve as an aortic valve.