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一种具有抗炎、抗凝血和促进内皮细胞增殖功能的绿原酸策略,用于生物人工心脏瓣膜。

A chlorogenic acid functional strategy of anti-inflammation, anti-coagulation and promoted endothelial proliferation for bioprosthetic artificial heart valves.

机构信息

National Engineering Research Center of Clean Technology in Leather Industry, Sichuan University, Chengdu 610065, China.

National Engineering Research Center for Biomaterials, Sichuan University, Chengdu 610065, China.

出版信息

J Mater Chem B. 2023 Mar 22;11(12):2663-2673. doi: 10.1039/d2tb02407a.

Abstract

Heart valve replacement has become an optimal choice for the treatment of severe heart valve disease. At present, most commercial bioprosthetic heart valves (BHVs) are made from porcine pericardium or bovine pericardium treated with glutaraldehyde. Nevertheless, due to the toxicity of residual aldehyde groups left after glutaraldehyde cross-linking, these commercial BHVs exhibit poor biocompatibility, calcification, risk of coagulation and endothelialization difficulty, which greatly affects the durability of the BHVs and shortens their service life. In this work, based on a chlorogenic acid functional anti-inflammation, anti-coagulation and endothelialization strategy and dual-functional non-glutaraldehyde cross-linking reagent OX-CO, a kind of functional BHV material OX-CA-PP has been developed from OX-CO cross-linked porcine pericardium (OX-CO-PP) followed by the convenient modification of chlorogenic acid through a reactive oxygen species (ROS) sensitive borate ester bond. The functionalization of chlorogenic acid can reduce the risk of valve leaf thrombosis and promote endothelial cell proliferation, which is beneficial to the formation of a long-term interface with good blood compatibility. Meanwhile, such a ROS responsive behavior can trigger intelligent release of chlorogenic acid on-demand to achieve the inhibition of acute inflammation at the early stage of implantation. The and experimental results show that the functional BHV material OX-CA-PP exhibits superior anti-inflammation, improved anti-coagulation, minimal calcification and promoted proliferation of endothelial cells, showing that this non-glutaraldehyde functional strategy has great potential for the application of BHVs and providing a promising reference for other implanted biomaterials.

摘要

心脏瓣膜置换已成为治疗严重心脏瓣膜病的最佳选择。目前,大多数商业生物瓣(BHV)都是用戊二醛处理过的猪心包或牛心包制成的。然而,由于戊二醛交联后残留醛基的毒性,这些商业 BHV 表现出较差的生物相容性、钙化、凝血风险和内皮化困难,这极大地影响了 BHV 的耐久性并缩短了其使用寿命。在这项工作中,基于一种绿原酸功能抗炎、抗凝血和内皮化策略和双功能非戊二醛交联试剂 OX-CO,从 OX-CO 交联的猪心包(OX-CO-PP)开发了一种功能性 BHV 材料 OX-CA-PP,随后通过活性氧(ROS)敏感硼酸酯键方便地修饰绿原酸。绿原酸的功能化可以降低瓣膜叶血栓形成的风险,促进内皮细胞增殖,有利于形成具有良好血液相容性的长期界面。同时,这种 ROS 响应行为可以按需智能释放绿原酸,以实现植入早期急性炎症的抑制。体内和体外实验结果表明,功能化 BHV 材料 OX-CA-PP 表现出优异的抗炎、改善的抗凝血、最小的钙化和促进内皮细胞增殖的能力,表明这种非戊二醛功能化策略在 BHV 的应用中具有巨大的潜力,并为其他植入生物材料提供了有前景的参考。

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