负载肝素和钛酸钡的聚偏氟乙烯静电纺丝膜制备及其抗凝抗菌性能

doi:10.19894/j.issn.1000-0518.250091

摘要/Abstract

摘要：

血液接触类医疗器械在临床上具有重要的应用，广泛用于血管支架、人工血管、瓣膜和血液净化设备等，对保障人类健康发挥着重要作用。然而，在使用过程中，这些器械往往会引起机体的免疫反应和血栓形成，导致治疗效果不佳。此外，植入过程中器械表面可能接触细菌，进而引发感染。因此，开发具有抗凝和抗菌功能的功能性表面十分迫切。本文针对血液接触类器械在使用过程中产生血栓和细菌感染的问题，通过静电纺丝技术，在基底材料表面制备了负载肝素和钛酸钡的聚偏氟乙烯（PVDF）微纳纤维膜（PVDF/Hep/BaTiO₃），通过扫描电子显微镜、傅里叶变换红外光谱和X射线光电子能谱对材料表面进行表征，并对构建表面的生物相容性、血液相容性和抗菌能力进行了研究，结果表明：微纳纤维中含有肝素，具有良好的抗血栓生成能力，使血小板粘附量降低60%；微纳纤维的仿细胞外基质结构和肝素共同作用，使材料促内皮细胞增殖能力提高20%；同时，微纳纤维的溶血率低于5%，细胞活力高于90%，体现出良好的生物相容性。此外，微纳纤维中钛酸钡和PVDF能够协同增强压电效应，在超声预处理后，能够杀死90%以上的大肠杆菌和金黄葡萄球菌。因此，PVDF/Hep/BaTiO₃微纳纤维改性膜具有较好的促细胞增殖能力、抗凝能力和抗菌能力，为血液接触类器械的多功能化提供了一种简单、有效的表面改性策略。

关键词: 肝素, 聚偏氟乙烯, 抗凝, 抗菌, 压电性能

Abstract:

Blood-contacting medical devices hold significant clinical applications， including vascular stents， artificial blood vessels， valves， and blood purification equipment， playing a vital role in safeguarding human health. However， these devices often trigger immune responses and thrombus formation during use， leading to suboptimal therapeutic outcomes. Additionally， bacterial contact on device surfaces during implantation may result in infections. Consequently， there is an urgent need to develop blood-contacting device surfaces with dual anticoagulant and antibacterial functionalities. This study addresses the issues of thrombosis and bacterial infections that can occur during the use of blood contact devices. Using electrospinning technology， a polyvinylidene fluoride （PVDF） micro-nano fiber membrane loaded with heparin and barium titanate （PVDF/Hep/BaTiO₃） was prepared on the surface of a substrate material. The material's surface was characterized using scanning electron microscopy， Fourier transform infrared spectroscopy， and X-ray photoelectron spectroscopy. The study investigated the biocompatibility， hemocompatibility， and antibacterial properties of the constructed surface. The results showed that the micro-nano fibers containing heparin exhibit excellent anti-thrombotic properties， reducing platelet adhesion by 60%. The extracellular matrix-like structure of the micro-nano fibers， combined with heparin， enhances the material's ability to promote endothelial cell proliferation by 20%. Additionally， the hemolysis rate of the micro-nano fibers is less than 5%， and the cell viability is over 90%， indicating good biocompatibility. Furthermore， the barium titanate and PVDF in the micro-nano fibers work together to enhance the piezoelectric effect， killing over 90% of bacteria after ultrasonic pretreatment.Thus， the PVDF/Hep/BaTiO₃ micro/nano fiber-modified membrane exhibits excellent cell proliferation promotion， anticoagulation， and antibacterial properties， providing a simple yet effective surface modification strategy for multifunctional optimization of blood-contacting medical devices.

Key words: Heparin, Polyvinylidene fluoride, Anticoagulant, Antibacterial, Piezoelectric effect

中图分类号:

O631

郭传宇, 孙丽宇, 关兴华, 石强. 负载肝素和钛酸钡的聚偏氟乙烯静电纺丝膜制备及其抗凝抗菌性能[J]. 应用化学, 2025, 42(12): 1636-1648.

Chuan-Yu GUO, Li-Yu SUN, Xing-Hua GUAN, Qiang SHI. Heparin/Barium Titanate-Loaded PVDF Electrospun Membranes： Fabrication， Anticoagulant， and Antibacterial Performance[J]. Chinese Journal of Applied Chemistry, 2025, 42(12): 1636-1648.

图/表 13

图1 （A） PU、（B） PVDF和（C） PVDF/Hep/BaTiO3表面的SEM图像；（D） PVDF和（E） PVDF/Hep/BaTiO3微纳纤维改性膜直径大小及分布

Fig.1 SEM image of the surface of （A） PU，（B） PVDF and （C） PVDF/Hep/BaTiO3； Diameter size and distribution of （D） PVDF and （E） PVDF/Hep/BaTiO3

图2 PU、PVDF、PVDF/Hep/BaTiO3和BaTiO3的FT-IR谱图

Fig.2 FT-IR spectra of PU， PVDF， PVDF/Hep/BaTiO3 and BaTiO3

图3 PVDF和PVDF/Hep/BaTiO3的XPS光谱图和F1s谱图

Fig.3 XPS and F1s spectra of PVDF and PVDF/Hep/BaTiO3

图4 PU、PVDF和PVDF/Hep/BaTiO3的水接触角分析图

Fig.4 Water contact angle analysis of PU， PVDF and PVDF/Hep/BaTiO3

图5 PVDF和PVDF/Hep/BaTiO3微纳纤维改性膜的（A）压电电压和（B）压电电流

Fig.5 （A） Piezoelectric voltage and （B） piezoelectric current of PVDF and PVDF/Hep/BaTiO3

图6 与PU、PVDF和PVDF/Hep/BaTiO3共培养24 h后的L929细胞的活/死荧光染色图像（绿色荧光代表Calcein AM，为活细胞；红色荧光代表PI，为死细胞）

Fig.6 Live/dead fluorescence staining images of L929 cells co-cultured with PU， PVDF and PVDF/Hep/BaTiO3 for 24 h （green fluorescence represents Calcein AM， which is live cells； red fluorescence represents PI， which is dead cells）

图7 与PU、PVDF和PVDF/Hep/BaTiO3共培养24和48 h后L929细胞的的细胞活力

Fig.7 Viability of L929 cells was determined after co-cultivation with PU， PVDF and PVDF/Hep/BaTiO3 for 24 and 48 h

图8 PU、PVDF和PVDF/Hep/BaTiO3的溶血率

Fig.8 Hemolysis analysis of PU， PVDF and PVDF/Hep/BaTiO3

图9 与PU、PVDF和PVDF/Hep/BaTiO3共培养24和48 h后，激光共聚焦显微镜下样品表面的HUVEC形态

Fig.9 Morphology of HUVEC on the surface of samples after co-cultivation with PU， PVDF and PVDF/Hep/BaTiO3 for 24 and 48 h was observed under laser confocal microscope

图10 与PU、PVDF和PVDF/Hep/BaTiO3共培养24和48 h后HUVEC细胞的增殖情况

Fig.10 Proliferation of HUVEC cells after co-cultivation with PU， PVDF and PVDF/Hep/BaTiO3 for 24 and 48 h

图11 PU、PVDF和PVDF/Hep/BaTiO3的（A）蛋白质粘附和（B）BCI

Fig.11 （A） Protein adhesion data on the surfaces and （B） blood clotting index of PU， PVDF and PVDF/Hep/BaTiO3

图12 PU、PVDF和PVDF/Hep/BaTiO3的血小板粘附半定量结果（490 nm）

Fig.12 Half quantitative results of platelet adhesion of PU， PVDF and PVDF/Hep/BaTiO3（490 nm）

图13 超声处理前后PU、PVDF和PVDF/Hep/BaTiO3样品对金黄色葡萄球菌和大肠杆菌的抑菌效果图片及抑菌率

Fig.13 Pictures and efficiency of antibacterial effect for PU， PVDF and PVDF/Hep/BaTiO3 samples against S.aureus and E.coli before and after ultrasonic treatment

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