Design and fabrication of a biomimetic vascular scaffold promoting in situ endothelialization and tunica media regeneration
Design and fabrication of a biomimetic vascular scaffold promoting in situ endothelialization and tunica media regeneration
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促进原位内皮化和中膜再生的仿生血管支架的设计和制造
DOI：
10.1021/acsabm.8b00269
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发表时间：
2018
影响因子：
4.7
通讯作者：
Mo Xiumei
中科院分区：
文献类型：
--
作者：
Wu Tong;Zhang Jialing;Wang Yuanfei;Sun Binbin;Yin Meng;Bowlin Gary L;Mo Xiumei
由于模拟血管的天然结构的性质，多层血管支架可以被认为在再生血管组织中是有利的。然而，目前存在有限的小直径血管支架，其整合了天然图尼卡内膜（抗血栓和快速内皮化）和图尼卡中膜（平滑肌细胞（SMC）的排列和向内生长，能够促进血管再生和功能的结构元件）的特定特征。为了解决这个问题，我们开发了一种改进的静电纺丝方法，能够制造一个双层血管支架与2毫米的内径和研究thein体内操作和再生能力，使用大鼠腹主动脉，与2个月的植入期。血管支架由聚（1-丙交酯-共-己内酯）/胶原（PLCL/COL）纳米纤维和无纺纱线制成，分别包括管腔层和中间层。将肝素和抗⑶ 133抗体（HEP/⑶ 133）掺入到包含腔层的PLCL/COL纳米纤维中。机械表征证明了双层支架的顺应性，其与人隐静脉相当，并且比市售的e-PTFE移植物有所改善。掺入的组分（HEP/CD 133）在近40天的时间内释放，在此期间，纳米纤维和纤维纱线保持其结构。此外，释放的肝素最初有助于管腔抗凝功能，而掺入的抗CD 133抗体促进了新生内膜的形成。此外，SMC增殖并渗透到整个纤维纱线的外部结构中。体内评价表明，单层内皮细胞（CD 31阳性）以及排列和浸润的平滑肌组织（α-SMA阳性）分别在制造的支架的内层和外层再生，证明了模仿天然血管的再生结构的能力。总之，功能化的双层支架可以被看作是一个有前途的候选人在原位血管组织再生。
Multilayered vascular scaffolds may be considered advantageous in regenerating vascular tissues due to the nature of mimicking the native structure of a blood vessel. However, there are currently limited small-diameter vascular scaffolds integrating the specific features of native tunica intima (anti-thrombus and rapid endothelialization) and tunica media (the alignment and ingrowth of smooth muscle cells (SMCs), structural elements capable of promoting vascular regeneration and function). To address this limitation, we developed a modified electrospinning method capable of fabricating a bilayer vascular scaffold with a 2-mm inner diameter and investigated thein vivoperformance and regenerative capacity using a rat abdominal aorta, with a 2-month implantation period. The vascular scaffold was fabricated from poly(l-lactide-co-caprolactone)/collagen (PLCL/COL) nanofibers and nanofiber yarns, comprising the luminal and medial layers, respectively. Heparin and anti-CD133 antibody (HEP/CD133) were incorporated into the PLCL/COL nanofibers comprising the luminal layer. The mechanical characterization demonstrated compliance of the bilayer scaffold, which was comparable to the human saphenous vein and improved over commercially available e-PTFE grafts. The incorporated components (HEP/CD133) were released over a period of nearly 40 days, during which the nanofibers and nanofiber yarns maintained their structure. Moreover, the released heparin contributed to lumen anticoagulation functionality initially, and the incorporated anti-CD133 antibody promoted the development of a neo-intima. In addition, SMCs proliferated and penetrated throughout the entire nanofiber yarn outer structure.In vivoevaluations demonstrated that a monolayer of endothelial cells (CD31 positive), as well as the aligned and infiltrated smooth muscle tissues (α-SMA positive), were regenerated on the inner and outer layers of the fabricated scaffold, respectively, demonstrating the capacity to regenerate structures mimicking native blood vessels. In conclusion, the functionalized bilayer scaffold can be viewed as a promising candidate forin situvascular tissue regeneration.