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通过双键交联功能化的生物心脏瓣膜,提高生物相容性和抗血栓形成性。

A functionalized biological heart valve by double bond crosslinking with enhanced biocompatibility and antithrombogenicity.

机构信息

National Engineering Research Center for Biomaterials, Sichuan University, No. 29, Wangjiang Road, Chengdu 610064, China.

Venus Medtech (Hangzhou) Inc., Hangzhou, China.

出版信息

J Mater Chem B. 2022 Dec 14;10(48):10001-10017. doi: 10.1039/d2tb02218d.

Abstract

With the advancement of minimally invasive interventional therapy, biological heart valves (BHVs) have been extensively used in clinics. However, BHVs are generally prone to degeneration within 10-15 years after implantation due to defects including cytotoxicity, immune response, calcification and thrombosis, which are closely related to glutaraldehyde-crosslinking. In this work, we prepared a functionalized BHV through the polymerization of methacrylated porcine pericardium and 2-hydroxyethyl methacrylate to avoid and overcome the defects of glutaraldehyde-crosslinked BHVs. The functionalized BHV was proven to be stable against enzymatic degradation and compatible towards HUVECs. After implantation in rats subcutaneously, a significantly mitigated immune response and reduced calcification were observed in the functionalized BHV. With the grafting of hydrophilic 2-hydroxyethyl methacrylate polymers, the antithrombogenicity of BHV was markedly enhanced by resisting the unfavorable adhesion of blood components. Moreover, the hydrodynamics of the functionalized BHV totally conformed to ISO 5840-3 under a wide range of simulated physiological conditions. These results indicate that the functionalized BHV with enhanced biocompatibility, anticalcification property and antithrombogenicity exhibited a low risk of degeneration and should be explored for further application.

摘要

随着微创介入治疗的发展,生物心脏瓣膜(BHVs)已在临床上广泛应用。然而,BHVs 在植入后 10-15 年内通常容易发生退化,其缺陷包括细胞毒性、免疫反应、钙化和血栓形成等,这些缺陷与戊二醛交联密切相关。在这项工作中,我们通过甲基丙烯酰化猪心包和 2-羟乙基甲基丙烯酸酯的聚合制备了一种功能化的 BHV,以避免和克服戊二醛交联 BHVs 的缺陷。功能化的 BHV 被证明可以抵抗酶降解,并且与 HUVECs 相兼容。在大鼠皮下植入后,功能化的 BHV 观察到明显减轻的免疫反应和减少的钙化。通过接枝亲水性 2-羟乙基甲基丙烯酸酯聚合物,BHV 的抗血栓形成性能得到显著增强,能够抵抗血液成分的不利黏附。此外,在广泛的模拟生理条件下,功能化的 BHV 的流体动力学完全符合 ISO 5840-3 标准。这些结果表明,具有增强的生物相容性、抗钙化性能和抗血栓形成性能的功能化 BHV 表现出较低的退化风险,应该进一步探索其应用。

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