Design and Simulation of Valvular Replacement Biomaterials

总结： 在可预见的未来，由异种移植生物材料制成的人工生物心脏瓣膜（BHV）仍将是主要的置换人工瓣膜设计。然而，BHV的耐久性仍然限于10-15年。失效通常是疲劳和/或组织矿化介导的瓣叶结构退化的结果。因此，与瓣膜设计细节（例如标准支架瓣膜、经皮输送）无关，开发具有改善耐久性的新型异种移植生物材料仍然是重要的临床目标。这代表了一个独特的心血管工程挑战，这是由血液接触时发生的极端瓣膜机械要求造成的。然而，目前的BHV评估仅依赖于器械级评价，这受到同时和高度耦合的生物材料力学行为和疲劳、瓣膜设计、血液动力学和钙化的混淆。因此，尽管BHV在临床上使用了数十年且日益普及，但在组件生物材料水平上，尚无可接受的评估和模拟BHV耐久性的方法。这种情况导致了目前BHV生物材料开发的停滞，限制了BHV耐久性的合理开发改进。我们假设，可以开发一种生物力学上严格和生理学上现实的体内方法，用于对固有BHV生物材料性能的机械理解。一旦开发出来，这种方法可以用于合理设计新型生物材料，显着提高BHV耐久性。虽然钙化预防尚未完全解决，但乙醇后处理已被证明可大大减少其发生。此外，其他人和我们已经表明，组织变性是BHV体外和体内耐久性有限的主要独立机制。因此，我们的重点将放在早期组织变性的机制和减少损伤积累的方法上，从而提高BHV的耐久性。

Summary: For the foreseeable future, bioprosthetic heart valves (BHV) fabricated from xenograft biomaterials will remain the dominant replacement prosthetic valve design. However, BHV durability remains limited to 10-15 years. Failure is usually the result of leaflet tructural deterioration mediated by fatigue and/or tissue mineralization. Thus, independent of valve design specifics (e.g. standard stented valve, percutaneous delivery), the development of novel xenograft biomaterials with improved durability remains an important clinical goal. This represents a unique cardiovascular engineering challenge resulting from the extreme valvular mechanical demands that occur with blood contact. Yet, current BHV assessment relies exclusively on device-level evaluations, which are confounded by simultaneous and highly coupled biomaterial mechanical behaviors and fatigue, valve design, hemodynamics, and calcification. Thus, despite decades of clinical BHV usage and growing popularity, there exists no acceptable method for assessing and simulating BHV durability at the component biomaterial level. This situation has contributed to the current stagnation in BHV biomaterial development, limiting rationally developed improvements in BHV durability. We hypothesize that a biomechanically rigorous and physiologically realistic in-vivo approach can be developed for a mechanistic understanding of intrinsic BHV biomaterial performance. Once developed, such an approach can be used to rationally design novel biomaterials that significantly improve BHV durability. While calcification prevention has not been completely solved, ethanol post-treatment has been shown to strongly reduce its onset. Moreover, others and we have shown that tissue degeneration is a major independent mechanism underlying BHV limited durability both in-vitro and in-vivo. Thus, our focus will be on mechanisms of early tissue degeneration and means to reduce damage accumulation, leading to improving BHV durability.