Covalent Self-Assembly of PEG and Heparin Improves Biological Performance of Electrospun Vascular Grafts for Carotid Artery Replacement

T. Zhu, Hongbing Gu, Hongmei Zhang, Hongsheng Wang, Huitang Xia, X. Mo, Jinglei Wu
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Abstract

Rapid endothelialization of small-diameter vascular grafts remains a significant challenge in clinical practice. In addition, compliance mismatch causes intimal hyperplasia and finally leads to graft failure. To achieve compliance match and rapid endothelialization, we synthesized low-initial-modulus poly(ester-urethane)urea (PEUU) elastomer and prepared it into electrospun tubular grafts and then functionalized the grafts with poly(ethylene glycol) (PEG) and heparin via covalent self-assembly. The PEG- and heparin-functionalized PEUU (PEUU@PEG-Hep) graft had comparable mechanical properties with the native blood vessel. In vitro data demonstrated that the grafts are of great cytocompatibility and blood compatibility. Covalent self-assembly of PEG and heparin significantly promoted the adhesion, spreading, and proliferation of human umbilical vein endothelial cells (HUVECs) and upregulated the expression of vascular endothelial cell-related genes, as well as increased the capability of grafts in preventing platelet deposition. In vivo assessments indicated good biocompatibility of the PEUU@PEG-Hep graft as it did not induce severe immune responses. Replacement of resected carotid artery with the PEUU@PEG-Hep graft in a rabbit model showed that the graft was capable of rapid endothelialization, initiated vascular remodeling, and maintained patency. This study demonstrates the synergistic effects of compliance match and efficacious antithrombosis of synthetic grafts for blood vessel regeneration.
聚乙二醇和肝素共价自组装提高电纺丝血管移植物颈动脉置换术的生物学性能
在临床实践中,小直径血管移植的快速内皮化仍然是一个重大挑战。此外,顺应性错配导致内膜增生,最终导致移植物失败。为了实现顺应性匹配和快速内皮化,我们合成了低初始模量聚(酯-聚氨酯)尿素(PEUU)弹性体,并将其制备成电纺丝管状接枝,然后用聚乙二醇(PEG)和肝素通过共价自组装对接枝进行功能化。聚乙二醇和肝素功能化的PEUU (PEUU@PEG-Hep)移植物具有与天然血管相当的机械性能。体外实验结果表明,移植物具有良好的细胞相容性和血液相容性。聚乙二醇与肝素共价自组装显著促进人脐静脉内皮细胞(HUVECs)的粘附、扩散和增殖,上调血管内皮细胞相关基因的表达,增强移植物抗血小板沉积能力。体内评估表明PEUU@PEG-Hep移植物具有良好的生物相容性,因为它不会引起严重的免疫反应。在兔模型中,用PEUU@PEG-Hep移植物替代切除的颈动脉,表明移植物能够快速内皮化,启动血管重塑,并保持通畅。本研究证明了顺应性匹配和有效抗血栓形成对血管再生的协同作用。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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