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环形排列纤维引导体内功能性新动脉再生。

Circumferentially aligned fibers guided functional neoartery regeneration in vivo.

机构信息

State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Collaborative Innovation Center of Chemical Science and Engineering (Tianjin), College of Life Science, Nankai University, Tianjin 300071, China.

Tianjin State Key Laboratory of Modern Chinese Medicine, Tianjin University of Traditional Chinese Medicine, Tianjin, China.

出版信息

Biomaterials. 2015 Aug;61:85-94. doi: 10.1016/j.biomaterials.2015.05.024. Epub 2015 May 16.

Abstract

An ideal vascular graft should have the ability to guide the regeneration of neovessels with structure and function similar to those of the native blood vessels. Regeneration of vascular smooth muscle cells (VSMCs) with circumferential orientation within the grafts is crucial for functional vascular reconstruction in vivo. To date, designing and fabricating a vascular graft with well-defined geometric cues to facilitate simultaneously VSMCs infiltration and their circumferential alignment remains a great challenge and scarcely reported in vivo. Thus, we have designed a bi-layered vascular graft, of which the internal layer is composed of circumferentially aligned microfibers prepared by wet-spinning and an external layer composed of random nanofibers prepared by electrospinning. While the internal circumferentially aligned microfibers provide topographic guidance for in vivo regeneration of circumferentially aligned VSMCs, the external random nanofibers can offer enhanced mechanical property and prevent bleeding during and after graft implantation. VSMCs infiltration and alignment within the scaffold was then evaluated in vitro and in vivo. Our results demonstrated that the circumferentially oriented VSMCs and longitudinally aligned ECs were successfully regenerated in vivo after the bi-layered vascular grafts were implanted in rat abdominal aorta. No formation of thrombosis or intimal hyperplasia was observed up to 3 month post implantation. Further, the regenerated neoartery exhibited contraction and relaxation property in response to vasoactive agents. This new strategy may bring cell-free small diameter vascular grafts closer to clinical application.

摘要

理想的血管移植物应具有引导具有与天然血管相似结构和功能的新血管再生的能力。在移植物内使血管平滑肌细胞(VSMCs)以周向取向再生对于体内功能性血管重建至关重要。迄今为止,设计和制造具有明确几何线索的血管移植物以促进 VSMCs 渗透及其周向排列仍然是一个巨大的挑战,并且在体内很少有报道。因此,我们设计了一种双层血管移植物,其内层由通过湿法纺丝制备的周向排列的微纤维组成,外层由通过静电纺丝制备的随机纳米纤维组成。虽然内部周向排列的微纤维为体内周向排列的 VSMCs 再生提供了地形导向,但外部随机纳米纤维可以提供增强的机械性能并防止移植物植入期间和之后出血。然后在体外和体内评估了支架内 VSMCs 的渗透和排列。我们的结果表明,在将双层血管移植物植入大鼠腹主动脉后,体内成功地再生了周向取向的 VSMCs 和纵向排列的 ECs。植入后 3 个月内未观察到血栓形成或内膜增生。此外,再生的新动脉表现出对血管活性药物的收缩和舒张特性。这种新策略可能使无细胞小直径血管移植物更接近临床应用。

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