Stasiak Joanna R, Serrani Marta, Biral Eugenia, Taylor James V, Zaman Azfar G, Jones Samantha, Ness Thomas, De Gaetano Francesco, Costantino Maria Laura, Bruno Vito D, Suleiman Saadeh, Ascione Raimondo, Moggridge Geoff D
Department of Chemical Engineering and Biotechnology, University of Cambridge, Cambridge, UK.
Biomater Sci. 2020 Aug 21;8(16):4467-4480. doi: 10.1039/d0bm00412j. Epub 2020 Jul 1.
Clinically available prosthetic heart valves are life-saving, but imperfect: mechanical valves requiring anticoagulation therapy, whilst bioprosthetic valves have limited durability. Polymer valves offer the prospect of good durability without the need for anticoagulation. We report the design and development of a polymeric heart valve, its bench-testing at ISO standards, and preliminary extra-vivo and in vivo short-term feasibility. Prototypes were manufactured by injection moulding of styrenic block copolymers to achieve anisotropic mechanical properties. Design was by finite element stress-strain modelling, which has been reported previously, combined with feedback from bench and surgery-based testing using various combinations of materials, valve geometry and processing conditions. Bench testing was according to ISO 5840:2015 standards using an in vitro cardiovascular hydrodynamic testing system and an accelerated fatigue tester. Bench comparisons were made with a best-in-class bio-prosthesis. Preliminary clinical feasibility evaluations included extra-vivo and short-term (1-24 hours) in vivo testing in a sheep model. The optimised final prototype met the requirements of ISO standards with hydrodynamic performance equivalent to the best-in-class bioprosthesis. Bench durability of greater than 1.2 billion cycles (30 years equivalent) was achieved (still ongoing). Extra-vivo sequential testing (n = 8) allowed refinement of external diameter, 3D shape, a low profile, flexibility, suturability, and testing of compatibility to magnetic resonance imaging and clinical sterilisation. In vivo short-term (1-24 hours) feasibility (n = 3) confirmed good suturability, no mechanical failure, no trans-valvular regurgitation, competitive trans-valvular gradients, and good biocompatibility at histopathology. We have developed and tested at ISO standards a novel prosthetic heart valve featuring competitive bench-based hydrodynamics and durability, well beyond the ISO requirements and comparable to a best-in-class bioprosthesis. In vivo short-term feasibility testing confirmed preliminary safety, functionality and biocompatibility, supporting progression to a long-term efficacy trial.
临床可用的人工心脏瓣膜能挽救生命，但并不完美：机械瓣膜需要抗凝治疗，而生物瓣膜的耐用性有限。聚合物瓣膜有望在无需抗凝的情况下实现良好的耐用性。我们报告了一种聚合物心脏瓣膜的设计与开发、其按照ISO标准进行的台架测试以及初步的体外和体内短期可行性研究。原型通过苯乙烯嵌段共聚物的注塑成型制造，以实现各向异性的机械性能。设计采用有限元应力应变建模（此前已有报道），并结合了使用各种材料组合、瓣膜几何形状和加工条件进行的台架测试及基于手术的测试反馈。台架测试按照ISO 5840:2015标准，使用体外心血管流体动力学测试系统和加速疲劳测试仪进行。与一流的生物瓣膜进行了台架比较。初步临床可行性评估包括在绵羊模型中的体外和短期（1 - 24小时）体内测试。优化后的最终原型符合ISO标准要求，流体动力学性能与一流的生物瓣膜相当。实现了超过12亿次循环（相当于30年）的台架耐久性（仍在进行中）。体外连续测试（n = 8）使得能够优化外径、三维形状、低轮廓、柔韧性、可缝合性，并测试与磁共振成像和临床灭菌的兼容性。体内短期（1 - 24小时）可行性研究（n = 3）证实了良好的可缝合性、无机械故障、无瓣膜反流、具有竞争力的跨瓣膜梯度以及组织病理学上良好的生物相容性。我们已经按照ISO标准开发并测试了一种新型人工心脏瓣膜，其具有基于台架的具有竞争力的流体动力学和耐久性，远超ISO要求，且与一流的生物瓣膜相当。体内短期可行性测试证实了初步的安全性、功能性和生物相容性，支持推进至长期疗效试验。
