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An atorvastatin calcium and poly(L-lactide-co-caprolactone) core-shell nanofiber-covered stent to treat aneurysms and promote reendothelialization.
Acta Biomaterialia ( IF 9.4 ) Pub Date : 2020-05-19 , DOI: 10.1016/j.actbio.2020.04.044
Jin Chu 1 , Li Chen 2 , Zengshuo Mo 3 , Gary L Bowlin 4 , Benjamin A Minden-Birkenmaier 4 , Yosry Morsi 5 , Ali Aldalbahi 6 , Mohamed El-Newehy 6 , Wu Wang 2 , Xiumei Mo 1
Affiliation  

Aneurysmal subarachnoid hemorrhage is a common complication caused by an intracranial aneurysm that can lead to hemorrhagic stroke, brain damage, and death. Knowing this clinical situation, the purpose of this study was to develop a controlled-release stent covered with a core-shell nanofiber mesh, fabricated by emulsion electrospinning, for the treatment of aneurysms. By encapsulating atorvastatin calcium (AtvCa) in the inner of poly (L-lactide-co-caprolactone) (PLCL) nanofibers, the release period of AtvCa was effectively extended. The morphology and inner structure of the core-shell nanofibers were observed by scanning electron microscopy (SEM) and transmission electron microscopy (TEM), respectively. The release of AtvCa from the nanofiber system continued for more than ten weeks without a significant initial burst release. The nanofiber mesh structure degraded gradually but maintained its fiber morphology before neovascularization. The results of this study further elucidated the reendothelialization mechanism of AtvCa by analyzing the nitric oxide (NO) expression from seeded HUVECs. The in vivo studies demonstrated that the PLCL-AtvCa covered stents were capable of separating the aneurysm dome from the blood circulation, leading to the abolishment of the aneurysm. Moreover, the AtvCa controlled release promoted the in vitro proliferation of HUVECs on the nanofiber meshes, and the PLCL-AtvCa covered stents induced in vivo neovascularization.

Statement of Significance

Intracranial aneurysms are pathological dilatations of blood vessels that have developed an abnormally weak wall structure, thus prone to rupture.

Covered stents had been demonstrated to be a method for the treatment of intracranial aneurysm. We prepared a controlled-release stent covered with a core-shell nanofiber mesh, fabricated by emulsion electrospinning, which encapsulated atorvastatin calcium in the inner portion of nanofibers. The results of this study further elucidated the reendothelialization mechanism of AtvCa by analyzing the nitric oxide (NO) expression from seeded HUVECs. The generated AtvCa-load covered stents separated the aneurysm dome from the blood circulation, and keep long-term patency of the parent artery. But also induced neovascularization, thus provide further protection against recurrence of aneurysms after nanofiber meshes degradation.



中文翻译:

阿托伐他汀钙和聚(L-丙交酯-己内酯)核-壳纳米纤维覆盖的支架可治疗动脉瘤并促进血管内皮再生。

动脉瘤性蛛网膜下腔出血是颅内动脉瘤引起的常见并发症,可导致出血性中风,脑损伤和死亡。了解这种临床情况,本研究的目的是开发一种覆盖有核-壳纳米纤维网的控释支架,该支架由乳剂静电纺丝制成,用于治疗动脉瘤。通过将阿托伐他汀钙(AtvCa)封装在聚(L-丙交酯-己内酯)(PLCL)纳米纤维的内部,有效延长了AtvCa的释放时间。分别通过扫描电子显微镜(SEM)和透射电子显微镜(TEM)观察核-壳纳米纤维的形态和内部结构。AtvCa从纳米纤维系统的释放持续了十多个星期,而没有明显的初始爆发释放。纳米纤维网状结构逐渐降解,但在新血管形成之前保持其纤维形态。这项研究的结果通过分析种子HUVEC中一氧化氮(NO)的表达进一步阐明了AtvCa的再内皮化机制。的体内研究表明,PLCL-AtvCa覆盖的支架能够将动脉瘤穹顶与血液循环分离,从而消除动脉瘤。此外,AtvCa控释促进了HUVEC在纳米纤维网上的体外增殖,PLCL-AtvCa覆盖的支架诱导了体内新血管形成。

重要声明

颅内动脉瘤是血管的病理性扩张,已经发展出异常脆弱的壁结构,因此容易破裂。

Covered stents had been demonstrated to be a method for the treatment of intracranial aneurysm. We prepared a controlled-release stent covered with a core-shell nanofiber mesh, fabricated by emulsion electrospinning, which encapsulated atorvastatin calcium in the inner portion of nanofibers. The results of this study further elucidated the reendothelialization mechanism of AtvCa by analyzing the nitric oxide (NO) expression from seeded HUVECs. The generated AtvCa-load covered stents separated the aneurysm dome from the blood circulation, and keep long-term patency of the parent artery. But also induced neovascularization, thus provide further protection against recurrence of aneurysms after nanofiber meshes degradation.

更新日期:2020-06-24
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