Matsushita Hiroshi, Inoue Takahiro, Abdollahi Sara, Yeung Enoch, Ong Chin Siang, Lui Cecillia, Pitaktong Isaree, Nelson Kevin, Johnson Jed, Hibino Narutoshi
Division of Cardiac Surgery, Johns Hopkins Hospital, Baltimore, Md.
Nanofiber Solutions, LLC, Hilliard, Ohio.
JVS Vasc Sci. 2020 Apr 11;1:100-108. doi: 10.1016/j.jvssci.2020.03.003. eCollection 2020.
Prosthetic grafts are often needed in open vascular procedures. However, the smaller diameter prosthetic grafts (<6 mm) have low patency and often result in complications from infection. Tissue-engineered vascular grafts (TEVGs) are a promising replacement for small diameter prosthetic grafts. TEVGs start as a biodegradable scaffold to promote autologous cell proliferation and functional neotissue regeneration. Owing to the limitations of graft materials; however, most TEVGs are rigid and easily kinked when implanted in limited spaces, which precludes clinical application. We have developed a novel corrugated nanofiber graft to prevent kinking.
TEVGs with corrugated walls (5-mm internal diameter by 10 cm length) were created by electrospinning a blend of poly-ε-caprolactone and poly(L-lactide-co-caprolactone). The biodegradable grafts were then implanted between the carotid artery and the external jugular vein in a U-shape using an ovine model. TEVGs were implanted on both the left and right side of a sheep (n = 4, grafts = 8). The grafts were explanted 1 month after implantation and inspected with mechanical and histologic analyses. Graft patency was confirmed by measuring graft diameter and blood flow velocity using ultrasound, which was performed on day 4 and every following week after implantation.
All sheep survived postoperatively except for one sheep that died of acute heart failure 2 weeks after implantation. The graft patency rate was 87.5% (seven grafts out of eight) with one graft becoming occluded in the early phase after implantation. There was no significant kinking of the grafts. Overall, endothelial cells were observed in the grafts 1 month after the surgeries without graft rupture, calcification, or aneurysmal change.
Our novel corrugated nanofiber vascular graft displayed neotissue formation without kinking in large animal model.
在开放性血管手术中常常需要使用人工血管移植物。然而，较小直径的人工血管移植物（<6毫米）通畅率较低，且常引发感染并发症。组织工程血管移植物（TEVG）有望替代小直径人工血管移植物。TEVG起始于可生物降解支架，以促进自体细胞增殖和功能性新组织再生。然而，由于移植物材料的局限性，大多数TEVG质地坚硬，植入有限空间时容易扭结，这限制了其临床应用。我们研发了一种新型波纹状纳米纤维移植物以防止扭结。
通过静电纺丝聚-ε-己内酯和聚（L-丙交酯-共-己内酯）的混合物，制备出内径为5毫米、长度为10厘米的带波纹壁的TEVG。然后，使用绵羊模型将可生物降解移植物呈U形植入颈动脉和颈外静脉之间。在一只绵羊的左右两侧各植入一个TEVG（n = 4，移植物 = 8）。植入1个月后取出移植物，进行力学和组织学分析。通过超声测量移植物直径和血流速度来确认移植物通畅情况，在植入后第4天及之后每周进行一次超声检查。
除一只绵羊在植入后2周死于急性心力衰竭外，所有绵羊术后均存活。移植物通畅率为87.5%（8个移植物中有7个），有一个移植物在植入后早期发生闭塞。移植物没有明显扭结。总体而言，术后1个月在移植物中观察到内皮细胞，且没有移植物破裂、钙化或动脉瘤样改变。
我们的新型波纹状纳米纤维血管移植物在大型动物模型中显示出无扭结的新组织形成。
