Guo Feng, Liu Yunen, Jiao Kai, Yang Rui, Hou Mingxiao, Zhang Xing
Institute of Metal Research, Chinese Academy of Sciences, Shenyang, Liaoning 110016, China.
School of Materials Science and Engineering, University of Science and Technology of China, Hefei, Anhui 230026, China.
ACS Appl Bio Mater. 2020 Feb 17;3(2):838-847. doi: 10.1021/acsabm.9b00902. Epub 2020 Jan 2.
Currently, the only treatment for moderate and severe aortic valve calcification disease is valve replacement. The clinical use of bioprosthetic heart valves (BHVs) is limited because of device failure caused by structural degeneration, such as the calcification of BHV leaflets. In the present study, poly(ethylene glycol) diacrylate (PEGDA) was incorporated with zwitterion (2-[methacryloyloxy]ethyl)dimethyl-(3-sulfopropyl) ammonium hydroxide (SBMA) forming a balanced charged network, which was further used to modify decellularized heart valves (DHV) and improve anticalcification properties. Valvular prostheses were designed and manufactured to comply with the requirements of ISO-5840 for valve fluid dynamics (i.e., effective orifice area = 1.9 cm, regurgitant fraction = 1.5% for Φ25 mm surgical valve at heart stroke of 80 mL). Weight loss of artificial heart valves (PEGDA-SBMA-DHV) was less than 5.5% after enzymatic hydrolysis for 12 h. No obvious calcification was observed in artificial heart valves that were modified with PEGDA-SBMA, whereas calcification was found in decellularized heart valves and the PEGDA-modified group. Furthermore, histological staining results indicated that artificial heart valves (PEGDA-SBMA-DHV) with a balanced charged network elicited negligible inflammation. Thus, balanced charged networks of PEGDA-SBMA with cationic and anionic groups can prevent the transportation of Ca ions and enzyme molecules, conferring efficient anticalcification properties to artificial heart valves.
目前，中重度主动脉瓣钙化疾病的唯一治疗方法是瓣膜置换。生物人工心脏瓣膜（BHVs）在临床中的应用受到限制，因为其会因结构退化导致装置故障，如BHV瓣叶钙化。在本研究中，聚乙二醇二丙烯酸酯（PEGDA）与两性离子（2-甲基丙烯酰氧基乙基）二甲基-（3-磺丙基）氢氧化铵（SBMA）结合形成平衡电荷网络，该网络进一步用于修饰去细胞心脏瓣膜（DHV）并改善抗钙化性能。设计并制造的瓣膜假体符合ISO-5840对瓣膜流体动力学的要求（即有效开口面积 = 1.9平方厘米，对于25毫米的手术瓣膜，在80毫升心搏量时反流分数 = 1.5%）。人工心脏瓣膜（PEGDA-SBMA-DHV）在酶水解12小时后的重量损失小于5.5%。在PEGDA-SBMA修饰的人工心脏瓣膜中未观察到明显钙化，而去细胞心脏瓣膜和PEGDA修饰组中则发现有钙化。此外，组织学染色结果表明，具有平衡电荷网络的人工心脏瓣膜（PEGDA-SBMA-DHV）引发的炎症可忽略不计。因此，具有阳离子和阴离子基团的PEGDA-SBMA平衡电荷网络可阻止钙离子和酶分子的运输，赋予人工心脏瓣膜高效的抗钙化性能。
