Matsushita Hiroshi, Hayashi Hidenori, Nurminsky Katherine, Dunn Tyler, He Yusheng, Pitaktong Isaree, Koda Yojiro, Xu Shanxiu, Nguyen Vivian, Inoue Takahiro, Rodgers Daniel, Nelson Kevin, Johnson Jed, Hibino Narutoshi
Section of Cardiac Surgery, Biological Sciences Division, the University of Chicago, Chicago, IL.
Nanofiber Solutions, LLC, Hilliard, OH.
JVS Vasc Sci. 2022 Feb 22;3:182-191. doi: 10.1016/j.jvssci.2022.01.002. eCollection 2022.
Many patients who require hemodialysis treatment will often require a prosthetic graft after multiple surgeries. However, the patency rate of grafts currently available commercially has not been satisfactory. Tissue engineering vascular grafts (TEVGs) are biodegradable scaffolds created to promote autologous cell proliferation and functional neotissue regeneration and, accordingly, have antithrombogenicity. Therefore, TEVGs can be an alternative prosthesis for small diameter grafts. However, owing to the limitations of the graft materials, most TEVGs are rigid and can easily kink when implanted in limited spaces, precluding future clinical application. Previously, we developed a novel corrugated nanofiber graft to prevent graft kinking. Reinforcement of these grafts to ensure their safety is required in a preclinical study. In the present study, three types of reinforcement were applied, and their effectiveness was examined using large animals.
In the present study, three different reinforcements for the graft composed of corrugated poly-ε-caprolactone (PCL) blended with poly(L-lactide-co-ε-caprolactone) (PLCL) created with electrospinning were evaluated: 1) a polydioxanone suture, 2) a 2-0 polypropylene suture, 3) a polyethylene terephthalate/polyurethane (PET/PU) outer layer, and PCL/PLCL as the control. These different grafts were then implanted in a U-shape between the carotid artery and jugular vein in seven ovine models for a total of 14 grafts during a 3-month period. In evaluating the different reinforcements, the main factors considered were cell proliferation and a lack of graft dilation, which were evaluated using ultrasound examinations and histologic and mechanical analysis.
No kinking of the grafts occurred. Overall, re-endothelialization was observed in all the grafts at 3 months after surgery without graft rupture or calcification. The PCL/PLCL grafts and PCL/PLCL grafts with a polydioxanone suture showed high cell infiltration; however, they had become dilated 10 weeks after surgery. In contrast, the PCL/PLCL graft with the 2-0 suture and the PCL/PLCL graft covered with a PET/PU layer did not show any graft expansion. The PCL/PLCL graft covered with a PET/PU layer showed less cell infiltration than that of the PCL/PLCL graft.
Reinforcement is required to create grafts that can withstand arterial pressure. Reinforcement with suture materials has the potential to maintain cell infiltration into the graft, which could improve the neotissue formation of the graft.
许多需要血液透析治疗的患者在多次手术后通常需要植入人工血管移植物。然而，目前市售移植物的通畅率并不理想。组织工程血管移植物（TEVGs）是一种可生物降解的支架，旨在促进自体细胞增殖和功能性新组织再生，因此具有抗血栓形成性。所以，TEVGs可作为小口径移植物的替代假体。然而，由于移植物材料的局限性，大多数TEVGs质地坚硬，植入有限空间时容易扭结，这阻碍了其未来的临床应用。此前，我们开发了一种新型波纹状纳米纤维移植物以防止移植物扭结。在临床前研究中需要对这些移植物进行加固以确保其安全性。在本研究中，应用了三种类型的加固方法，并使用大型动物对其有效性进行了检测。
在本研究中，对由静电纺丝制备的波纹状聚己内酯（PCL）与聚（L-丙交酯-共-己内酯）（PLCL）混合而成的移植物的三种不同加固方法进行了评估：1）聚二氧六环酮缝线，2）2-0聚丙烯缝线，3）聚对苯二甲酸乙二酯/聚氨酯（PET/PU）外层，以及PCL/PLCL作为对照。然后将这些不同的移植物以U形植入7只绵羊模型的颈动脉和颈静脉之间，在3个月的时间里共植入14个移植物。在评估不同的加固方法时，主要考虑的因素是细胞增殖和移植物无扩张，这通过超声检查以及组织学和力学分析进行评估。
移植物未发生扭结。总体而言，术后3个月时在所有移植物中均观察到再内皮化，且没有移植物破裂或钙化。PCL/PLCL移植物和带有聚二氧六环酮缝线的PCL/PLCL移植物显示出较高的细胞浸润；然而，它们在术后10周出现了扩张。相比之下，带有2-0缝线的PCL/PLCL移植物和覆盖有PET/PU层的PCL/PLCL移植物未显示出任何移植物扩张。覆盖有PET/PU层的PCL/PLCL移植物的细胞浸润少于PCL/PLCL移植物。
需要进行加固以制造能够承受动脉压力的移植物。用缝合材料进行加固有可能维持细胞向移植物内浸润，这可能会改善移植物的新组织形成。
