Yu Tao, Pu Hongxia, Chen Xiaotong, Kong Qunshou, Chen Chong, Li Gaocan, Jiang Qing, Wang Yunbing
National Engineering Research Center for Biomaterials and College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.
National Engineering Research Center for Biomaterials and College of Biomedical Engineering, Sichuan University, 29 Wangjiang Road, Chengdu 610064, China.
Acta Biomater. 2023 Apr 1;160:45-58. doi: 10.1016/j.actbio.2023.02.002. Epub 2023 Feb 9.
Valvular heart disease is a major threat to human health and transcatheter heart valve replacement (THVR) has emerged as the primary treatment option for severe heart valve disease. Bioprosthetic heart valves (BHVs) with superior hemodynamic performance and compressibility have become the first choice for THVR, and more BHVs have been requested for clinical use in recent years. However, several drawbacks remain for the commercial BHVs cross-linked by glutaraldehyde, including calcification, thrombin, poor biocompatibility and difficulty in endothelialization, which would further reduce the BHVs' lifetime. This study developed a dual-functional non-glutaraldehyde crosslinking reagent OX-VI, which can provide BHV materials with reactive double bonds (CC) for further bio-function modification in addition to the crosslinking function. BHV material PBAF@OX-PP was developed from OX-VI treated porcine pericardium (PP) after the polymerization with 4-vinylbenzene boronic acid and the subsequent modification of poly (vinyl alcohol) and fucoidan. Based on the functional anti-coagulation and endothelialization strategy and dual-functional crosslinking reagent, PBAF@OX-PP has better anti-coagulation and anti-calcification properties, higher biocompatibility, and improved endothelial cells proliferation when compared to Glut-treated PP, as well as the satisfactory mechanical properties and enhanced resistance effect to enzymatic degradation, making it a promising candidate in the clinical application of BHVs. STATEMENT OF SIGNIFICANCE: Transcatheter heart valve replacement (THVR) has become the main solution for severe valvular heart disease. However, bioprosthetic heart valves (BHVs) used in THVR exhibit fatal drawbacks such as calcification, thrombin and difficulty for endothelialization, which are due to the glutaraldehyde crosslinking, resulting in a limited lifetime to 10-15 years. A new non-glutaraldehyde cross-linker OX-VI has been designed, which can not only show great crosslinking ability but also offer the BHVs with reactive double bonds (CC) for further bio-function modification. Based on the dual-functional crosslinking reagent OX-VI, a versatile modification strategy was developed and the BHV material (PBAF@OX-PP) has been developed and shows significantly enhanced anticoagulant, anti-calcification and endothelialization properties, making it a promising candidate in the clinical application of BHVs.
心脏瓣膜病是对人类健康的重大威胁，经导管心脏瓣膜置换术（THVR）已成为严重心脏瓣膜病的主要治疗选择。具有优异血流动力学性能和可压缩性的生物人工心脏瓣膜（BHVs）已成为THVR的首选，近年来临床对BHVs的需求也越来越大。然而，通过戊二醛交联的商用BHVs仍存在一些缺点，包括钙化、凝血、生物相容性差和内皮化困难，这将进一步缩短BHVs的使用寿命。本研究开发了一种双功能非戊二醛交联剂OX-VI，除了交联功能外，它还能为BHV材料提供反应性双键（C═C），以便进一步进行生物功能修饰。用OX-VI处理猪心包（PP），然后与4-乙烯基苯硼酸聚合，随后对聚乙烯醇和岩藻依聚糖进行改性，从而制备出BHV材料PBAF@OX-PP。基于功能性抗凝血和内皮化策略以及双功能交联剂，与戊二醛处理的PP相比，PBAF@OX-PP具有更好的抗凝血和抗钙化性能、更高的生物相容性、改善的内皮细胞增殖能力，以及令人满意的机械性能和增强的抗酶降解效果，使其成为BHVs临床应用中一个有前景的候选材料。重要意义声明：经导管心脏瓣膜置换术（THVR）已成为严重心脏瓣膜病的主要解决方案。然而，用于THVR的生物人工心脏瓣膜（BHVs）存在致命缺点，如钙化、凝血和内皮化困难，这些都是由戊二醛交联导致的，使其使用寿命限制在10至15年。一种新型非戊二醛交联剂OX-VI已被设计出来，它不仅具有强大的交联能力，还能为BHVs提供反应性双键（C═C），以便进一步进行生物功能修饰。基于双功能交联剂OX-VI，开发了一种通用的改性策略，并制备出BHV材料（PBAF@OX-PP），该材料显示出显著增强的抗凝、抗钙化和内皮化性能，使其成为BHVs临床应用中一个有前景的候选材料。
