A completely biological "off-the-shelf" arteriovenous graft that recellularizes in baboons
A completely biological "off-the-shelf" arteriovenous graft that recellularizes in baboons
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DOI：
10.1126/scitranslmed.aan4209
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发表时间：
2017-11-01
影响因子：
17.1
通讯作者：
Tranquillo, Robert T.
中科院分区：
文献类型：
--
作者：
Syedain, Zeeshan H.;Graham, Melanie L.;Tranquillo, Robert T.
传统用于血液透析的假体动静脉移植物（AVGs）与自体静脉移植物相比，原发性通畅率较低，感染风险增加。我们用牛纤维蛋白凝胶包裹新生人皮成纤维细胞，然后将其脱细胞，对其进行组织工程培养。这种移植物既是“现成的”（无生命的），又是完全生物的。在狒狒模型中，在上臂腋窝-头侧或腋窝-臂侧AVG构建过程中，评估了直径为6mm，长度约为15cm的移植物的血液透析通路。给予每日抗血小板治疗。移植物在1、2、3和6个月时进行超声评估和插管，然后拔出进行分析。排除在模型发育过程中迅速凝血的头静脉流出的移植物，3- 6个月的原发性通畅率分别为83%（5 / 6）和60%（3 / 5）。在外植体中，发现未移植移植物具有广泛的再细胞化（包括光滑素阳性的平滑肌细胞，其管腔表面有正在发育的内皮）。我们没有观察到钙化、破裂强度丧失或流出口狭窄，而这些是其他移植材料常见的失效模式。没有明显的免疫反应。因此，我们证明了一种现成的非细胞和完全生物的AVG的功效。
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 axillarybrachial 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.