Research ArticleTissue Engineering

A completely biological “off-the-shelf” arteriovenous graft that recellularizes in baboons

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Science Translational Medicine  01 Nov 2017:
Vol. 9, Issue 414, eaan4209
DOI: 10.1126/scitranslmed.aan4209

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Growing grafts for hemodialysis

Patients undergoing hemodialysis for renal failure often receive an arteriovenous fistula, a connection between a vein and an artery. These surgical connections fail or cannot be attempted in some patients with compromised vasculature, who instead require vein grafts. As an alternative to autologous or synthetic grafts, Syedain et al. used a tissue engineering approach to generate vascular grafts from sacrificial fibrin scaffolds and human fibroblasts. Decellularized grafts were implanted into baboons and tested as hemodialysis access points. Over the course of 6 months, the grafts were recellularized with host cells and maintained sufficient burst pressure without evidence of immune rejection. Pending additional testing, these grafts represent an additional surgical option for hemodialysis access.

Abstract

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.

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