National Engineering Research Center for Biomaterials, Sichuan University, No. 29, Wangjiang Road, Chengdu 610064, China.
Venus Medtech (Hangzhou) Inc., Hangzhou, China.
J Mater Chem B. 2022 Dec 14;10(48):10001-10017. doi: 10.1039/d2tb02218d.
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.
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。