Department of Biomedical Engineering, University of Minnesota, Minneapolis, MN 55455, USA.
Preclinical Research Center, University of Minnesota, Minneapolis, MN 55455, USA.
Sci Transl Med. 2017 Nov 1;9(414). doi: 10.1126/scitranslmed.aan4209.
Prosthetic arteriovenous grafts (AVGs) conventionally used for hemodialysis are associated with inferior primary patency rates and increased risk of infection compared with autogenous vein grafts. We tissue-engineered an AVG grown from neonatal human dermal fibroblasts entrapped in bovine fibrin gel that is then decellularized. This graft is both "off-the-shelf" (nonliving) and completely biological. Grafts that are 6 mm in diameter and about 15 cm in length were evaluated in a baboon model of hemodialysis access in an axillary-cephalic or axillary-brachial upper arm AVG construction procedure. Daily antiplatelet therapy was given. Grafts underwent both ultrasound assessment and cannulation at 1, 2, 3, and 6 months and were then explanted for analysis. Excluding grafts with cephalic vein outflow that rapidly clotted during development of the model, 3- and 6-month primary patency rates were 83% (5 of 6) and 60% (3 of 5), respectively. At explant, patent grafts were found to be extensively recellularized (including smoothelin-positive smooth muscle cells with a developing endothelium on the luminal surface). We observed no calcifications, loss of burst strength, or outflow stenosis, which are common failure modes of other graft materials. There was no overt immune response. We thus demonstrate the efficacy of an off-the-shelf AVG that is both acellular and completely biological.
用于血液透析的假体动静脉移植物 (AVG) 与自体静脉移植物相比，其原发性通畅率较低，感染风险增加。我们使用牛纤维蛋白凝胶包埋的新生儿人真皮成纤维细胞构建了一种组织工程 AVG，然后对其进行去细胞化处理。这种移植物既“现成的”（无生命的），又完全是生物的。评估了直径为 6 毫米、长约 15 厘米的移植物，这些移植物在腋头或腋臂上臂的血液透析通路的狒狒模型中进行了构建。每天给予抗血小板治疗。在 1、2、3 和 6 个月时，对移植物进行超声评估和插管，然后进行移植以进行分析。排除模型开发过程中头静脉流出迅速凝结的移植物，3 个月和 6 个月的原发性通畅率分别为 83%（5/6）和 60%（3/5）。在移植时，发现通畅的移植物被广泛再细胞化（包括在管腔表面有发育中的内皮的 smoothelin 阳性平滑肌细胞）。我们没有观察到钙化、爆裂强度丧失或流出道狭窄，这是其他移植物材料的常见失效模式。没有明显的免疫反应。因此，我们证明了一种现成的、无细胞且完全生物的 AVG 的有效性。
