A completely biological "off-the-shelf" arteriovenous graft that recellularizes in baboons. Sci Transl Med 2017 Nov 01;9(414)
Date
11/03/2017Pubmed ID
29093182DOI
10.1126/scitranslmed.aan4209Scopus ID
2-s2.0-85032831624 (requires institutional sign-in at Scopus site) 109 CitationsAbstract
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.
Author List
Syedain ZH, Graham ML, Dunn TB, O'Brien T, Johnson SL, Schumacher RJ, Tranquillo RTAuthor
Ty Blink Dunn MD Professor in the Surgery department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AnimalsArteriovenous Shunt, Surgical
Catheterization
Cattle
Coronary Angiography
Endothelial Cells
Humans
Immunity
Implants, Experimental
Kaplan-Meier Estimate
Male
Papio
Ultrasonography
Vascular Patency