PDF(Pubmed)
Abstract：
Biotubes are autologous tubular tissues developed within a patient\'s body through in-body tissue architecture, and they demonstrate high potential for early clinical application as a vascular replacement. In this pilot study, we used large animals to perform implantation experiments in preparation for preclinical testing of Biotube. The biological response after Biotube implantation was histologically evaluated. The designed Biotubes (length: 50 cm, internal diameter: 4 mm, and wall thickness: 0.85 mm) were obtained by embedding molds on the backs of six goats for a predetermined period (1-5 months). The same goats underwent bypass surgery on the carotid arteries using Biotubes (average length: 12 cm). After implantation, echocardiography was used to periodically monitor patency and blood flow velocity. The maximum observation period was 6 months, and tissue analysis was conducted after graft removal, including the anastomosis. All molds generated Biotubes that exceeded the tensile strength of normal goat carotid arteries, and eight randomly selected Biotubes were implanted. Thrombotic occlusion occurred immediately postoperatively (1 tube) if anticoagulation was insufficient, and two tubes, with insufficient Biotube strength (<5 N), were ruptured within a week. Five tubes maintained patency for >2 months without aneurysm formation. The spots far from the anastomosis became stenosed within 3 months (3 tubes) when Biotubes had a wide intensity distribution, but the shape of the remaining two tubes remained unchanged for 6 months. The entire length of the bypass region was walled with an αSMA-positive cell layer, and an endothelial cell layer covered most of the lumen at 2 months. Complete endothelial laying of the luminal surface was obtained at 3 months after implantation, and a vascular wall structure similar to that of native blood vessels was formed, which was maintained even at 6 months. The stenosis was indicated to be caused by fibrin adhesion on the luminal surface, migration of repair macrophages, and granulation formation due to the overproliferation of αSMA-positive fibroblasts. We revealed the importance of Biotubes that are homogeneous, demonstrate a tensile strength > 5 N, and are implanted under appropriate antithrombotic conditions to achieve long-term patency of Biotube. Further, we clarified the Biotube regeneration process and the mechanism of stenosis. Finally, we obtained the necessary conditions for a confirmatory implant study planned shortly.
摘要：
生物管是通过体内组织结构在患者体内形成的自体管状组织，它们显示出早期临床应用作为血管置换的巨大潜力。在这项试点研究中，我们使用大型动物进行植入实验，为Biotube的临床前测试做准备。组织学评估Biotube植入后的生物学反应。设计的生物管（长度：50厘米，内径：4毫米，和壁厚：0.85mm）是通过将模具嵌入六只山羊的背部并持续预定时间（1-5个月）而获得的。相同的山羊使用Biotube（平均长度：12厘米）在颈动脉上进行了旁路手术。植入后,超声心动图用于定期监测通畅性和血流速度。最长观察期为6个月,并在去除移植物后进行组织分析，包括吻合.所有霉菌产生的生物管超过正常山羊颈动脉的拉伸强度，并植入了8个随机选择的生物管。如果抗凝治疗不足，术后立即发生血栓闭塞（1管），还有两根管子,Biotube强度不足（<5N），一周内就破裂了.5根管维持通畅>2个月,未形成动脉瘤。当Biotubes具有较宽的强度分布时，远离吻合口的斑点在3个月内变得狭窄（3管），但其余两个管的形状保持不变6个月。旁路区域的整个长度都被αSMA阳性细胞层围住，2个月时，内皮细胞层覆盖了大部分管腔。植入后3个月获得腔表面的完整内皮铺设，形成了类似于天然血管的血管壁结构，即使在6个月时也保持不变。狭窄是由管腔表面的纤维蛋白粘附引起的，修复巨噬细胞的迁移，和由于αSMA阳性成纤维细胞的过度增殖而形成的肉芽。我们揭示了同质生物管的重要性，证明抗拉强度>5N，并在适当的抗血栓条件下植入，以实现Biotube的长期开放。Further,我们阐明了Biotube的再生过程和狭窄的机制。最后,我们获得了短期内计划的验证性植入研究的必要条件.
