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用响应性肝素水凝胶涂层增强神经血管镍钛合金装置的抗血栓性

Enhancing thromboresistance of neurovascular nickel-titanium devices with responsive heparin hydrogel coatings.

作者信息

Maitz Manfred F, Kaiser Daniel P O, Cuberi Ani, Weich Hernández Rafaela, Mühl-Benninghaus Ruben, Tomori Toshiki, Gawlitza Matthias

机构信息

Max Bergmann Center of Biomaterials, Leibniz Institute of Polymer Research Dresden, Dresden, Sachsen, Germany

Institute of Neuroradiology, University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Sachsen, Germany

出版信息

J Neurointerv Surg. 2025 May 22;17(6):625-631. doi: 10.1136/jnis-2024-021836.

Abstract

BACKGROUND

Neurointerventional devices, particularly laser-cut thin-strut stents made of self-expanding nickel-titanium alloy, are increasingly utilized for endovascular applications in intracranial arteries and dural venous sinuses. Preventing thrombosis and stroke necessitates systemic anticoagulant and antiplatelet therapies with the risk of bleeding complications. Antithrombotic coatings present a promising solution.

METHODS

In this study, we investigated the potential of hydrogels composed of four-armed poly(ethylene glycol) (starPEG) and heparin, with or without coagulation-responsive heparin release, as coatings for neurovascular devices to mitigate blood clot formation. We evaluated the feasibility and efficacy of these coatings on neurovascular devices through in vitro Chandler-Loop assays and implantation experiments in the supra-aortic arteries of rabbits.

RESULTS

Stable and coagulation-responsive starPEG-heparin hydrogel coatings exhibited antithrombotic efficacy in vitro, although with a slightly reduced thromboprotection observed in vivo. Furthermore, the hydrogel coatings demonstrated robustness against shear forces encountered during deployment and elicited only marginal humoral and cellular inflammatory responses compared with the reference standards.

CONCLUSION

Heparin hydrogel coatings offer promising benefits for enhancing the hemocompatibility of neurointerventional devices made of self-expanding nickel-titanium alloy. The variance in performance between in vitro and in vivo settings may be attributed to differences in low- and high-shear blood flow conditions inherent to these models. These models may represent the differences in venous and arterial systems. Further optimization is warranted to tailor the hydrogel coatings for improved efficacy in arterial applications.

摘要

背景

神经介入装置,特别是由自膨胀镍钛合金制成的激光切割细支撑支架,越来越多地用于颅内动脉和硬脑膜静脉窦的血管内应用。预防血栓形成和中风需要进行全身抗凝和抗血小板治疗,但存在出血并发症的风险。抗血栓涂层是一种很有前景的解决方案。

方法

在本研究中,我们研究了由四臂聚乙二醇(starPEG)和肝素组成的水凝胶(有或无凝血反应性肝素释放)作为神经血管装置涂层以减轻血栓形成的潜力。我们通过体外钱德勒环试验和在兔主动脉弓的植入实验评估了这些涂层在神经血管装置上的可行性和有效性。

结果

稳定且具有凝血反应性的starPEG-肝素水凝胶涂层在体外表现出抗血栓功效,尽管在体内观察到血栓保护作用略有降低。此外,与参考标准相比,水凝胶涂层在展开过程中表现出对剪切力的耐受性,并且仅引起轻微的体液和细胞炎症反应。

结论

肝素水凝胶涂层为提高由自膨胀镍钛合金制成的神经介入装置的血液相容性提供了有前景的益处。体外和体内环境下性能的差异可能归因于这些模型固有的低剪切和高剪切血流条件的差异。这些模型可能代表了静脉和动脉系统的差异。需要进一步优化以调整水凝胶涂层,提高其在动脉应用中的疗效。

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