Pu Xinyun, Peng Xu, Shi Shubin, Feng Shaoxiong, Wei Xu, Gao Xi, Yu Xixun
College of Polymer Science and Engineering, Sichuan University, Chengdu 610065, P.R. China.
Experimental and Research Animal Institute, Sichuan University, Chengdu 610041, P.R. China.
ACS Biomater Sci Eng. 2025 Jan 13;11(1):634-648. doi: 10.1021/acsbiomaterials.4c01724. Epub 2025 Jan 3.
Valvular heart disease (VHD) poses a significant threat to human health, and the transcatheter heart valve replacement (THVR) is the best treatment for severe VHD. Currently, the glutaraldehyde cross-linked commercial bioprosthetic heart valves (BHVs) remain the first choice for THVR. However, the cross-linking by glutaraldehyde exhibits several drawbacks, including calcification, inflammatory reactions, and difficult endothelialization, which limits the longevity and applicability of BHVs. In this study, λ-carrageenan with anticoagulant function was modified by carboxymethylation into carboxymethyl λ-carrageenan (CM-λC); subsequently, CM-λC was used as a cross-linking agent to stabilize decellularized bovine pericardial tissue through amide bonds formed by a 1-(3-(Dimethylamino)propyl)-3-ethylcarbodiimide/-Hydroxysuccinimide (EDC/NHS)-catalyzed reaction between the amino functional groups within pericardium and the carboxyl group located on CM-λC. Lastly, the inclusion complex (CD/Rutin) (formed by encapsulating the rutin molecule through the hydrophobic cavity of the mono-(6-ethylenediamine-6-deoxy)-β-cyclodextrin) was immobilized onto above BHVs materials (λCar-BP) through the amidation reaction. The treated sample exhibited mechanical properties and collagen stability similar to those of GA-BP, except for improved flexibility. Because of the presence of sulfonic acid groups and absence of aldehyde group as well as the Rutin release from CD/Rutin immobilized onto BHVs, the hemocompatibility, anti-inflammatory, HUVEC-cytocompatibility, and anticalcification properties, of the CM-λC-fixed BP modified with CD/Rutin was significantly better than that of GA-BP. In summary, this nonaldehyde-based natural polysaccharide cross-linking strategy utilizing the combination of CM-λC and CD/Rutin provides a novel solution to obtain BHVs with durable and stable anticoagulant, anticalcification, and anti-inflammatory properties, and has a wide range of potential applications in improving the various properties of BHVs.
心脏瓣膜病（VHD）对人类健康构成重大威胁，经导管心脏瓣膜置换术（THVR）是治疗严重VHD的最佳方法。目前，戊二醛交联的商用生物人工心脏瓣膜（BHVs）仍是THVR的首选。然而，戊二醛交联存在一些缺点，包括钙化、炎症反应和内皮化困难，这限制了BHVs的使用寿命和适用性。在本研究中，具有抗凝功能的λ-卡拉胶通过羧甲基化修饰为羧甲基λ-卡拉胶（CM-λC）；随后，CM-λC用作交联剂，通过1-（3-（二甲氨基）丙基）-3-乙基碳二亚胺/ N-羟基琥珀酰亚胺（EDC/NHS）催化的心包内氨基官能团与CM-λC上羧基之间形成的酰胺键来稳定去细胞牛心包组织。最后，通过酰胺化反应将包合物（CD/芦丁）（通过单-（6-乙二胺-6-脱氧）-β-环糊精的疏水腔包封芦丁分子形成）固定在上述BHVs材料（λCar-BP）上。除了柔韧性提高外，处理后的样品表现出与GA-BP相似的机械性能和胶原稳定性。由于存在磺酸基团且不存在醛基以及固定在BHVs上的CD/芦丁释放芦丁，用CD/芦丁修饰的CM-λC固定的BP的血液相容性、抗炎性、人脐静脉内皮细胞（HUVEC）细胞相容性和抗钙化性能明显优于GA-BP。总之，这种利用CM-λC和CD/芦丁组合的非醛基天然多糖交联策略为获得具有持久稳定的抗凝、抗钙化和抗炎性能的BHVs提供了一种新的解决方案，在改善BHVs的各种性能方面具有广泛的潜在应用。
