现代纺织技术

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基于熔体近场直写的小直径抗凝人造血管制备及性能

  

  1. 1. 浙江理工大学服装学院,浙江杭州 310018;2. 浙江省人民医院,a.临床医学研究所,b.泌尿外科, 浙江杭州 310014
  • 基金资助:
    国家自然科学基金项目(52403054);浙江省重点研发计划项目(2023C01196)

Preparation and performance of anticoagulant small-diameter artificial blood vessels via melt electrowriting

  1. 1. School of Fashion Design & Engineering, Zhejiang Sci-Tech University, Hangzhou 310018, China; 2a. Institute of Clinical Medical Research; 2b. Department of Urology, Zhejiang Provincial People’s Hospital, Hangzhou 310014, China

摘要: 为解决小直径人造血管在顺应性匹配和抗血栓性能方面的不足,将熔体静电纺丝(MES)与熔融近场直写(MEW)技术相结合,在MES纤维膜表面沉积MEW纤维支架,构建出小直径复合人造血管,并对其进行肝素功能化修饰。采用红外光谱与紫外吸收光谱对血管表面肝素的接枝情况进行表征,并系统评估了其力学性能及抗凝血性能。结果表明:MEW支架有效增强了人造血管的力学性能,且肝素修饰未对其力学性能产生明显影响。经不同质量浓度肝素修饰后,人造血管的顺应性均符合不同类型天然血管的顺应性要求。肝素修饰后的人造血管表现出良好的细胞和血液相容性,其中在肝素质量浓度为3 mg/mL条件下修饰的样品展现出最优的抗凝性能。通过结构设计与表面修饰的协同作用,本研究成功制备了顺应性与天然血管相匹配且具有优异抗凝性能的小直径人造血管,可为其后续开发与临床应用提供参考。

关键词: 人造血管, 增材制造, 高精度打印, 顺应性, 抗凝血

Abstract: Cardiovascular diseases pose a serious threat to human health. Vascular grafting restores blood vessel function by replacing damaged segments. Currently, autologous blood vessels are the clinical gold standard for transplantation. However, they are limited in availability and may lead to additional complications. Synthetic artificial blood vessels offer a new solution for vascular replacement. Large-diameter artificial blood vessels (≥ 6 mm) have achieved clinical success. However, small-diameter artificial blood vessels (< 6 mm) still face challenges, such as poor compliance with native vessels and high risk of thrombosis. In this study, we use a hybrid fabrication method that combines melt electrospinning (MES) and melt electrowriting (MEW). We construct a small-diameter artificial blood vessel using polycaprolactone (PCL) as the base material. We modify the vessel surface with heparin to give it anticoagulant properties. We first confirm the successful grafting of heparin using infrared spectroscopy (qualitative) and ultraviolet spectroscopy (quantitative). Then we evaluate the surface wettability, mechanical properties, cell compatibility, and anticoagulant performance. The results show that heparin modification significantly improves surface hydrophilicity. The water contact angle decreases from 125.3° to 0°. The MEW scaffold improves the mechanical strength of the vessel. Heparin modification does not negatively affect the mechanical performance. We measure compliance by cyclic tensile tests. The compliance values are 9.71±0.42, 9.62±0.35, and 9.67±0.29 %/100mmHg. These values meet the compliance requirements of various native blood vessels. CCK-8 tests show that the cell viability of heparin-functionalized vascular grafts exceeds 80%, indicating good cytocompatibility. Hemolysis tests confirm that the hemolysis rates of the heparinized grafts remain below 5%, demonstrating favorable hemocompatibility. Clotting assay results indicate that the anticoagulant performance improves with increasing heparin concentration. Notably, no visible clot formation occurs within 6 minutes on the grafts modified with 3 mg/mL heparin, confirming the effective anticoagulant properties conferred by heparin functionalization. This study successfully constructs a small-diameter composite artificial blood vessel with anticoagulant function. It provides a technical and experimental basis for the development of small-diameter vascular grafts.

Key words: artificial blood vessel, additive manufacture, high-precision printing, compliance, anticoagulation

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