Heparin-Eluting Electrospun Nanofiber Yarns for Antithrombotic Vascular Sutures
Heparin-Eluting Electrospun Nanofiber Yarns for Antithrombotic Vascular Sutures
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肝素洗脱静电纺纳米纤维抗血栓血管缝合线
DOI：
10.1021/acsami.7b14888
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发表时间：
2018-03-14
影响因子：
9.5
通讯作者：
Lee, Jeoung Soo
中科院分区：
文献类型：
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作者：
Bae, Sooneon;DiBalsi, Michael J.;Lee, Jeoung Soo
血管的外科连接、吻合术是许多修复、移植和重建外科手术中的关键手术。然而，循环的有效恢复因病理性凝血（血栓形成）或由于过度细胞增殖导致的进行性闭塞而变得复杂，这通常导致额外的手术并增加患者的发病率和死亡率风险。已经测试了药物制剂来预防这些并发症，但许多药物具有不可接受的全身副作用。因此，需要一种以受控方式在损伤部位递送这些药物的替代方法。本研究的目的是开发由聚酯聚（丙交酯-共-乙交酯）（PLGA），聚（环氧乙烷）（PEO）和带正电荷的共聚物，聚（丙交酯-共-乙交酯）-接枝-聚乙烯亚胺（PgP）组成的静电纺丝纳米纤维，用于静电结合和释放肝素，作为抗血栓形成的微血管缝合线。以PLGA和支链聚乙烯亚胺（bPEI）之间的不同偶联比率合成PgP，以获得PgP（1）（类似于1个PLGA接枝到1个bPEI）和PgP（3.7）（类似于3.7个PLGA接枝到1个bPEI）。通过静电纺丝制备纳米纤维纱线（PLGA/PEO/PgP（1）和PLGA/PEO/PgP（3.7））。使用荧光素缀合的肝素（F-Hep）使带正电荷的纤维素纱线上的肝素固定化可视化，并且在PLGA/PEO/PgP（3.7）和PLGA/PEO/PgP（1）上固定化的F-Hep的量高于不含PgP的纱线（PLGA/PEO）。我们还发现，F-Hep从两种含Pgp的纱线中以持续的方式释放超过20天，而超过60%的F-Hep在4小时内从PLGA/PEO中释放。最后，我们观察到，含有PgP（1）和PgP（3.7）的肝素洗脱纤维纱线比不含PgP的纤维纱线显示出显著更长的凝血时间。PLGA/PEO/PgP（3.7）的凝血时间与游离肝素（0.5 μ g/mL）无显著差异。这些结果表明，肝素洗脱静电纺丝纱线可能为开发具有抗凝活性的微血管缝合线提供基础。
The surgical connection of blood vessels, anastomosis, is a critical procedure in many reparative, transplantation, and reconstructive surgical procedures. However, effective restoration of circulation is complicated by pathological clotting (thrombosis) or progressive occlusion due to excess cell proliferation that often leads to additional surgeries and increases morbidity and mortality risk for patients. Pharmaceutical agents have been tested to prevent these complications, but many have unacceptable systemic side effects. Therefore, an alternative approach to deliver these drugs at the site of injury in a controlled manner is necessary. The objective of this study was to develop electrospun nanofibers composed of polyester poly(lactide-co-glycolide) (PLGA), poly(ethylene oxide) (PEO), and positively charged copolymer, poly(lactide-co-glycolide)-graft-polyethylenimine (PgP) for electrostatic binding and release of heparin for application as an antithrombotic microvascular suture. PgP was synthesized with different coupling ratios between PLGA and branched polyethylenimine (bPEI) to obtain PgP(1) (similar to 1 PLGA grafted to 1 bPEI) and PgP(3.7) (similar to 3.7 PLGA grafted to 1 bPEI). Nanofiber yarns (PLGA/PEO/PgP(1) and PLGA/PEO/PgP(3.7)) were fabricated by electrospinning. Heparin immobilization on the positively charged nanofiber yarns was visualized using fluorescein-conjugated heparin (F-Hep), and the amount of immobilized F-Hep was higher on both PLGA/PEO/PgP(3.7) and PLGA/PEO/PgP(1) than yarns without PgP (PLGA/PEO). We also found that F-Hep was released from both PgP-containing yarns in a sustained manner over 20 days, while over 60% of F-Hep was released within 4 h from PLGA/PEO. Finally, we observed that heparin-eluting nanofiber yarns with both PgP(1) and PgP(3.7) showed significantly longer clotting times than nanofiber yarns without PgP. The clotting time of PLGA/PEO/PgP(3.7) was not significantly different than that of free heparin (0.5 mu g/mL). These results show that heparin-eluting electrospun nanofiber yarns may offer a basis for the development of microvascular sutures with anticoagulant activity.