National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, 610064, China.
Macromol Biosci. 2019 Jun;19(6):e1800390. doi: 10.1002/mabi.201800390. Epub 2019 Apr 5.
Bioprosthetic heart valves (BHVs) used in the clinic are mostly fixed by glutaraldehyde and the lack of endothelialization is a major problem for glutaraldehyde-fixed pericardia. Hyaluronic acid is a major glycosaminoglycan that exists in native heart valves. Coupled with its inherent biocompatibility, it may enhance endothelial adhesion and proliferation when associated with vascular endothelial growth factor (VEGF). In this study, an optimized system is developed to improve the endothelialization of glutaraldehyde-fixed pericardium. A hybrid pericardium with VEGF-loaded hyaluronic acid hydrogel coating is developed by the crosslinking of 1,4-butanediol diglycidyl ether. The adhesion and growth potential of human umbilical vein endothelial cells (HUVECs) on pericardia, platelet adhesion, and calcification by an in vivo rat subdermal implantation model are investigated. The results show improved HUVEC adhesion and proliferation, less platelet adhesion, and less calcification for hybrid pericardium by introducing the coating of VEGF-loaded hyaluronic acid hydrogel. Thus, the coating of VEGF-loaded hyaluronic acid hydrogel on pericardium is a promising approach to obtain bioprosthetic valves for clinical applications with increased endothelialization and antithrombotic and anticalcification properties.
临床上使用的生物心脏瓣膜（BHVs）大多通过戊二醛固定，而缺乏内皮化是戊二醛固定的心包膜的一个主要问题。透明质酸是一种主要的糖胺聚糖，存在于天然心脏瓣膜中。由于其固有的生物相容性，当与血管内皮生长因子（VEGF）结合时，它可能会增强内皮细胞的黏附和增殖。在这项研究中，开发了一种优化的系统来改善戊二醛固定的心包膜的内皮化。通过 1,4-丁二醇二缩水甘油醚的交联，开发了一种载有 VEGF 的透明质酸水凝胶涂层的杂交心包。通过体内大鼠皮下植入模型研究了心包上的人脐静脉内皮细胞（HUVEC）的黏附和生长潜力、血小板黏附和钙化。结果表明，通过引入载有 VEGF 的透明质酸水凝胶涂层，杂交心包的 HUVEC 黏附和增殖得到改善，血小板黏附和钙化减少。因此，在心包上涂覆载有 VEGF 的透明质酸水凝胶是一种很有前途的方法，可以获得具有增加的内皮化、抗血栓和抗钙化特性的临床应用的生物假体瓣膜。
