Hu Yage, Xiong Yao, Wei Yuan, Liu Jingze, Zheng Tiantian, Zheng Cheng, Li Gaocan, Luo Rifang, Yang Li, Zhang Fanjun, Wang Yunbing
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, PR China.
National Engineering Research Center for Biomaterials, College of Biomedical Engineering, Sichuan University, Chengdu 610064, PR China.
Acta Biomater. 2024 Dec;190:64-78. doi: 10.1016/j.actbio.2024.10.045. Epub 2024 Oct 30.
A series of polycarbonate silicone polyurethanes (SiPCUs) have been synthesized to develop elastomers with the mechanical properties, biostability, and biocompatibility required for artificial heart valve manufacturing. In these SiPCUs, the polar functional group 4,4'-dicyclohexylmethane diisocyanate (HMDI) was incorporated into the soft segment 1,6-poly (hexamethylene carbonate) diol (PCDL) to form the modified macromolecular diol, PCDL-HMDI-PCDL. The hard segment consisted of HMDI and the chain extenders 1,4-butanediol and 1,3-bis(4-hydroxybutyl)-1,1,3,3-tetramethyl disiloxane (BHTD). The synthesized PHC-PCUB improves the excessive microphase separation caused by the introduction of PDMS. This material possesses good physicochemical properties, long-term oxidative degradation stability, and comparatively low mechanical performance loss after degradation. Compared to the commercially available bioprosthetic heart valve (BHV) material Glut-PP, PHC-PCUB demonstrated enhanced biocompatibility, good thromboresistant properties, less calcification, and higher endothelial cell adhesion. Furthermore, valve prototypes fabricated with PHC-PCUB showed improved hemodynamic performance under various simulated conditions, highlighting the potential of PHC-PCUB as an advanced material for valve leaflets. STATEMENT OF SIGNIFICANCE: Artificial heart valves are crucial for treating valve diseases, and polyurethane-based valves present a promising alternative due to their durability, strong biocompatibility, and customizable properties. This study improves the biostability and post-degradation mechanical properties of siloxane polyurethanes by reducing the content of polydimethylsiloxane (PDMS) and adding modified diol (PCDL-HMDI-PCDL). By integrating hexamethylene diisocyanate (HMDI) and chain extenders, we developed polycarbonate siloxane polyurethanes (SiPCUs) that improve phase mixing, mechanical strength, and oxidative stability. These SiPCUs also exhibit good thromboresistance and calcification resistance, low cytotoxicity, and promote cell adhesion, positioning them as highly promising materials for heart valve leaflets, effectively addressing the limitations of current mechanical and bioprosthetic valves.
已合成了一系列聚碳酸酯硅氧烷聚氨酯（SiPCUs），以开发具有人工心脏瓣膜制造所需机械性能、生物稳定性和生物相容性的弹性体。在这些SiPCUs中，极性官能团4,4'-二环己基甲烷二异氰酸酯（HMDI）被引入软段1,6-聚（碳酸己二醇酯）二醇（PCDL）中，形成改性大分子二醇PCDL-HMDI-PCDL。硬段由HMDI和扩链剂1,4-丁二醇以及1,3-双（4-羟丁基）-1,1,3,3-四甲基二硅氧烷（BHTD）组成。合成的PHC-PCUB改善了因引入聚二甲基硅氧烷（PDMS）而导致的过度微相分离。这种材料具有良好的物理化学性质、长期氧化降解稳定性以及降解后相对较低的机械性能损失。与市售生物人工心脏瓣膜（BHV）材料Glut-PP相比，PHC-PCUB表现出增强的生物相容性、良好的抗血栓性能、较少的钙化以及更高的内皮细胞粘附性。此外，用PHC-PCUB制造的瓣膜原型在各种模拟条件下显示出改善的血流动力学性能，突出了PHC-PCUB作为瓣膜小叶先进材料的潜力。重要性声明：人工心脏瓣膜对于治疗瓣膜疾病至关重要，基于聚氨酯的瓣膜因其耐久性、强大的生物相容性和可定制性而成为一种有前途的替代品。本研究通过降低聚二甲基硅氧烷（PDMS）的含量并添加改性二醇（PCDL-HMDI-PCDL）来提高硅氧烷聚氨酯的生物稳定性和降解后机械性能。通过整合六亚甲基二异氰酸酯（HMDI）和扩链剂，我们开发了聚碳酸酯硅氧烷聚氨酯（SiPCUs），其改善了相混合、机械强度和氧化稳定性。这些SiPCUs还表现出良好的抗血栓性和抗钙化性、低细胞毒性并促进细胞粘附，使其成为心脏瓣膜小叶极具前景的材料，有效解决了当前机械瓣膜和生物人工瓣膜的局限性。
