School of Materials Science and Engineering, Beijing Institute of Technology, Beijing 100081, China.
Beijing Key Laboratory of Preclinical Research and Evaluation for Cardiovascular Implant Materials, Fuwai Hospital National Cardiovascular Center, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing 100037, China.
Biomater Adv. 2022 Feb;133:112628. doi: 10.1016/j.msec.2021.112628. Epub 2021 Dec 29.
Increasingly growing problems in vascular access for long-term hemodialysis lead to a considerable demand for synthetic small diameter vascular prostheses, which usually suffer from some drawbacks and are associated to high failure rates. Incorporating the concept of in situ tissue engineering (TE) into synthetic small diameter blood vessels, for example, thermoplastic poly(ether urethane) (TPU) ones, could provide an alternative approach for vascular access that profits from the advantages of excellent mechanical properties of synthetic polymer materials (early cannulation) and unique biointegration regeneration of autologous neovascular tissues (long-term fistulae). In this study, a kind of heparinized small diameter (d = 2.5 mm) TPU/poly(ε-caprolactone) (TPU/PCL-Hep) bi-layered blood vessels was electrospun with an inner layer of PCL and an outer layer of TPU. Afterward, the inner surface heparinization was conducted by coupling HN-PEG-NH to the corroded PCL layer and then heparin to the attached HN-PEG-NH via the EDCI/NHS chemistry. Herein a heparinized PCL inner layer could not only inhibit thrombosis, but also provide sufficient space for the neotissue regeneration via biodegradation with time. Meanwhile, a TPU outer layer could confer the vascular access the good mechanical properties, such as flexibility, viability and fitness of elasticity between the grafts and host blood vessels as evidenced by the adequate mechanical properties, such as compliance (4.43 ± 0.07%/ 100 mmHg), burst pressure (1447 ± 127 mmHg) and suture retention strength (1.26 ± 0.07 N) without blood seepage after implantation. Furthermore, a rabbit carotid aortic replacement model for 5 months was demonstrated 100% animal survival and 86% graft patency. Puncture assay also revealed the puncture resistance and self-sealing (hemostatic time < 2 min). Histological analysis highlighted neotissue regeneration, host cell infiltration and graft remodeling in terms of extracellular matrix turnover. Altogether, these results showed promising aspects of small diameter TPU/PCL-Hep bi-layered grafts for hemodialytic vascular access applications.
日益增长的长期血液透析血管通路问题导致对合成小直径血管假体的大量需求，但这些假体通常存在一些缺陷，并且失败率较高。例如，将原位组织工程 (TE) 的概念纳入合成小直径血管（例如热塑性聚（醚氨酯）（TPU））中，可以提供一种替代血管通路的方法，这种方法受益于合成聚合物材料的优异机械性能（早期插管）和自体新生血管组织的独特生物整合再生（长期瘘管）的优势。在这项研究中，采用静电纺丝技术制备了一种肝素化小直径（d = 2.5mm）TPU/聚（ε-己内酯）（TPU/PCL-Hep）双层血管，内层为 PCL，外层为 TPU。随后，通过将 HN-PEG-NH 偶联到腐蚀的 PCL 层上，并通过 EDCI/NHS 化学将肝素连接到附着的 HN-PEG-NH 上来进行内层肝素化。在这里，肝素化的 PCL 内层不仅可以抑制血栓形成，而且可以随着时间的推移通过生物降解为新生组织提供足够的再生空间。同时，TPU 外层可以赋予血管通路良好的机械性能，例如柔韧性、活力和弹性适应性，这可以从适当的机械性能（如顺应性（4.43±0.07%/100mmHg）、爆裂压力（1447±127mmHg）和缝合保留强度（1.26±0.07N））中得到证明，植入后没有血液渗漏。此外，通过 5 个月的兔颈动脉主动脉置换模型证明了 100%的动物存活率和 86%的移植物通畅率。穿刺试验还显示了穿刺阻力和自密封（止血时间<2min）。组织学分析突出了新生组织的再生、宿主细胞的浸润和细胞外基质转化方面的移植物重塑。总之，这些结果显示了小直径 TPU/PCL-Hep 双层移植物在血液透析血管通路应用中的有前途的方面。
