Nitric oxide-releasing vascular grafts: A therapeutic strategy to promote angiogenic activity and endothelium regeneration

Nitric oxide-releasing vascular grafts: A therapeutic strategy to promote angiogenic activity and endothelium regeneration
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DOI:
10.1016/j.actbio.2019.05.002
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发表时间:
2019-07-01
期刊:
影响因子:
9.7
通讯作者:
Mozafari, Masoud
Mozafari, Masoud
中科院分区:
工程技术1区
文献类型:
--
作者:
Kabirian, Fatemeh;Milan, Peiman Brouki;Mozafari, Masoud

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小直径血管移植物(SDVG)与感染和阻塞导致的失败发生率高相关。虽然几种血管移植物是市售的,但缺损部位的特定解剖差异需要基于患者的设计和制造。这种定制移植物的设计和制造可以通过3d打印技术来实现。本研究的目的是开发具有一氧化氮(NO)释放涂层的3D打印SDVG,以提高植入的成功率。SDVG由聚乳酸印刷,并用10重量%的S-亚硝基-N-乙酰基-D-青霉胺共混物涂覆到由聚(乙二醇)和聚己内酯组成的聚合物基底中。我们的结果表明,NO在生理范围(0.5-4 × 10(-10)mol.cm(-2).min(-1))内释放14天,并且NO释放涂层对革兰氏阳性和革兰氏阴性菌株显示出显著的抗菌潜力。结果表明,NO释放和对照移植物在体外和体内均具有生物相容性。有趣的是,与对照移植物相比,释放NO的SDVG显着增强了EC的增殖,并显着增强了EC的体外迁移。此外,释放NO的SDVG在体内显示出血管生成潜力,这可以进一步证明我们的体外研究结果。这些发现有望促进组织再生和定制血管植入物的整合,提高临床成功率。
Small-diameter vascular grafts (SDVGs) are associated with a high incidence of failure due to infection and obstruction. Although several vascular grafts are commercially available, specific anatomical differences of defect sites require patient-based design and fabrication. Design and fabrication of such custom-tailored grafts are possible with 3d-printing technology. The aim of this study is to develop 3d-printed SDVGs with a nitric oxide (NO)-releasing coating to improve the success rate of implantation. The SDVGs were printed from polylactic acid and coated with blending of 10 wt% S-nitroso-N-acetyl-D-penicillamine into the polymeric substrate consisting of poly (ethylene glycol) and polycaprolactone. Our results show that NO is released in the physiological range (0.5-4 x 10(-10) mol.cm(-2).min(-1)) for 14 days and NO-releasing coating showed significant antibacterial potential against Gram-positive and Gram-negative strains. It was shown that both NO-releasing and control grafts are biocompatible in vitro and in-vivo. Interestingly, the NO-releasing SDVGs dramatically enhanced ECs proliferation and significantly enhanced ECs migration in-vitro compared to control grafts. In addition, the NO-releasing SDVGs showed angiogenic potential in-vivo which can further prove the results of our in-vitro study. These findings are expected to facilitate tissue regeneration and integration of custom-made vascular implants with enhanced clinical success.Statement of significanceA series of 3d-printed small-diameter vascular grafts (SDVGs,