Development of a Novel Hierarchically Biofabricated Blood Vessel Mimic Decorated with Three Vascular Cell Populations for the Reconstruction of Small-Diameter Arteries
Development of a Novel Hierarchically Biofabricated Blood Vessel Mimic Decorated with Three Vascular Cell Populations for the Reconstruction of Small-Diameter Arteries
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DOI：
10.1002/adfm.202300621
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发表时间：
2023-11-03
影响因子：
19
通讯作者：
Madeddu，Paolo
中科院分区：
文献类型：
--
作者：
Carrabba，Michele;Fagnano，Marco;Madeddu，Paolo
可用移植物替代小直径动脉仍然是一个未满足的临床需求。本文报道了一种新型杂交组织工程血管移植物的验证方法，旨在匹配小尺寸动脉的自然结构。血管模拟物（BVM）包括一个由共电纺丝明胶和聚己内酯（PCL）纳米纤维（对应于动脉内膜）组成的内部导管，并由一层PCL排列的纤维（内部弹性膜）加强。利用旋转生物反应器将内皮细胞沉积在管腔表面。生物打印系统挤出两个同心的水凝胶层，水凝胶层分别含有血管平滑肌细胞和周细胞，形成中膜和外膜。半自动化的细胞化过程将生产和成熟时间缩短至6天。经机械性能、细胞活力、血液相容性和可缝合性评估后，BVM成功植入猪左肺动脉。BVM在植入后5周表现出良好的止血特性、承受血压的能力和通畅。这些有希望的数据为开发用于重建小直径血管的类动脉产品开辟了新的途径。
The availability of grafts to replace small‐diameter arteries remains an unmet clinical need. Here, the validated methodology is reported for a novel hybrid tissue‐engineered vascular graft that aims to match the natural structure of small‐size arteries. The blood vessel mimic (BVM) comprises an internal conduit of co‐electrospun gelatin and polycaprolactone (PCL) nanofibers (corresponding to the tunica intima of an artery), reinforced by an additional layer of PCL aligned fibers (the internal elastic membrane). Endothelial cells are deposited onto the luminal surface using a rotative bioreactor. A bioprinting system extrudes two concentric cell‐laden hydrogel layers containing respectively vascular smooth muscle cells and pericytes to create the tunica media and adventitia. The semi‐automated cellularization process reduces the production and maturation time to 6 days. After the evaluation of mechanical properties, cellular viability, hemocompatibility, and suturability, the BVM is successfully implanted in the left pulmonary artery of swine. Here, the BVM showed good hemostatic properties, capability to withstand blood pressure, and patency at 5 weeks post‐implantation. These promising data open a new avenue to developing an artery‐like product for reconstructing small‐diameter blood vessels.