Weber Carolyn, Reinhardt Stefanie, Eghbalzadeh Kaveh, Wacker Max, Guschlbauer Maria, Maul Alexandra, Sterner-Kock Anja, Wahlers Thorsten, Wippermann Jens, Scherner Max
Department of Cardiothoracic Surgery, University of Cologne, Cologne, Germany.
Department of Cardiothoracic Surgery, University of Cologne, Cologne, Germany.
J Vasc Surg. 2018 Dec;68(6S):177S-187S.e1. doi: 10.1016/j.jvs.2017.09.038. Epub 2017 Dec 18.
Despite the clinical success of large-diameter vascular grafts, synthetic grafts in small-diameter vessels are of limited use because of their poor patency rates. Previous experiments of our group provided evidence for good biocompatibility of bacterial nanocellulose (BNC) as a small-vessel graft in the carotid artery in sheep. However, the patency rate of our first-generation tubes after 3 months was only 50%. To advance our concept, we now used modified second-generation tubes with diminished wall thickness and a smoother inner surface to reduce the thrombogenic potential. The aim was to investigate mechanical characteristics of modified second-generation BNC tubes, to evaluate in vivo performance and biocompatibility, and to analyze patency rates.
We replaced the right carotid artery of 23 sheep with second-generation BNC tubes. Compared with our first-generation tubes, tubes were modified with different surface properties and diminished wall thickness (inner diameter, 4.0-5.0 mm; wall thickness, 1.0-2.5 mm; length, 100 mm) to generate a smoother inner surface with reduced thrombogenic potential and a more porous outer zone, allowing easier cell immigration.
At the end of the investigational period, BNC tubes were explanted and grafts were processed for histopathologic analysis. Histologic analysis revealed no acute signs of foreign body reaction such as immigration of giant cells or other acute inflammatory reaction and therefore provided evidence for good biocompatibility of the second-generation tubes. However, all grafts of the sheep without antiplatelet therapy were occluded after 9 months, whereas grafts in sheep receiving dual platelet inhibition showed a patency rate of 67% (six of nine grafts). Further modified grafts revealed a patency rate of 80% (four of five grafts remained open).
Patency rates of the second-generation tubes could be substantially improved compared with our first-generation tubes. However, poor patency rates of tissue-engineered blood vessels still limit their use in clinical studies. Further efforts in terms of in vitro and in vivo studies are essential to improve grafts of BNC.
尽管大口径血管移植物在临床上取得了成功，但小口径血管的合成移植物由于通畅率低，应用有限。我们小组之前的实验证明了细菌纳米纤维素（BNC）作为绵羊颈动脉小血管移植物具有良好的生物相容性。然而，我们第一代血管的3个月通畅率仅为50%。为了推进我们的理念，我们现在使用了改良的第二代血管，其壁厚减小，内表面更光滑，以降低血栓形成的可能性。目的是研究改良第二代BNC血管的力学特性，评估其体内性能和生物相容性，并分析通畅率。
我们用第二代BNC血管替换了23只绵羊的右侧颈动脉。与我们的第一代血管相比，第二代血管的表面特性不同，壁厚减小（内径4.0 - 5.0毫米；壁厚1.0 - 2.5毫米；长度100毫米），以产生更光滑的内表面，降低血栓形成的可能性，并形成更多孔的外层区域，便于细胞迁移。
在研究期结束时，取出BNC血管并对移植物进行组织病理学分析。组织学分析未发现异物反应的急性迹象，如巨细胞迁移或其他急性炎症反应，因此证明了第二代血管具有良好的生物相容性。然而，未接受抗血小板治疗的绵羊的所有移植物在9个月后均闭塞，而接受双重血小板抑制的绵羊的移植物通畅率为67%（9个移植物中有6个通畅）。进一步改良的移植物通畅率为80%（5个移植物中有4个保持开放）。
与第一代血管相比，第二代血管的通畅率有了显著提高。然而，组织工程血管的低通畅率仍然限制了它们在临床研究中的应用。在体外和体内研究方面进一步努力对于改进BNC移植物至关重要。
