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
  • Fig. 1. Pre-implant AVG appearance and physical properties.

    (A) Side view and (B) end-on view image of a 6-mm-diameter decellularized tissue-engineered vascular graft. (C) Trichrome-stained cross section of the graft showing circumferentially aligned collagen fibers (blue). (D) Picrosirius red–stained cross section under polarized light confirming collagen fiber orientation primarily in the circumferential direction. (E) Ultimate tensile strength (UTS) and modulus of the graft. (F) Burst pressure and (G) suture retention force with comparison to human internal mammary artery (IMA) (21). Scale bars, 200 μm.

  • Fig. 2. Kaplan-Meier diagram for all grafts that did not rapidly generate an occlusive clot.

    Percent graft patency is plotted as a function of time after implantation in baboons (n = 6).

  • Fig. 3. AVG implanted into a baboon model.

    (A) Graft image at implantation showing proximal anastomosis to axillary artery and distal anastomosis to brachial vein. (B) Ultrasound-based measurement of midgraft and distal graft diameter over the course of implantation. Color Doppler image of (C) distal graft-vein junction at 3 months, (D) midgraft at 6 months, and (E) distal graft-vein junction at 6 months (heat map scale in meters per second). (F) Angiogram image of the graft with contrast dye at 6 months. White arrows indicate distal anastomosis. Paired symbols (* and #) in the plot indicate P < 0.05.

  • Fig. 4. Explanted AVG appearance and physical properties.

    Side view at (A) 3-month and (B) 6-month explantation showing loose connective tissue grown onto abluminal surface. End-on view at (C) 3-month and (D) 6-month explantation. (E) Graft thickness of the pre-implant grafts and explanted grafts in distal regions that were cannulated (shaded) and proximal region (solid). Hematoxylin and eosin (H&E) stain of midgraft section at (F) 3-month and (G) 6-month explantation. (H) Graft burst pressure measurement comparison of the pre-implant grafts with proximal segments (solid) and distal cannulated segments (shaded). Paired symbols (* and #) in plots indicate P < 0.05. In H&E images, luminal surface is marked with an asterisk (*). Scale bars, 100 μm.

  • Fig. 5. Histology of explanted AVG.

    Sections from midgraft region with trichrome stain, fibrin immunostaining, and calcification indicator von Kossa stain at (A to C) 3-month (n = 1) and (D to I) 6-month (n = 3) explantation. Luminal surface is marked with an asterisk (*). Scale bars, 200 μm.

  • Fig. 6. Cellularity of explanted AVG.

    Sections from midgraft region stained for the interstitial cell marker vimentin, the myofibroblast/smooth muscle cell marker α–smooth muscle actin (α-SMA), and the endothelial marker CD31 at (A to C) 3-month (n = 1) and (D to I) 6-month (n = 3) explantation. Insets show staining for the mature smooth muscle cell marker smoothelin. Luminal surface is marked with an asterisk (*). Scale bars in black, 200 μm; scale bars in red, 50 μm.

  • Fig. 7. Assessment of systemic immune response to implanted AVG.

    Plots of peripheral blood mononuclear cell (PBMC; T cell) proliferation (A) (n = 19, including 3 regrafts) and IgE, IgG, and IgM blood concentrations (B to D) (n = 49, including 3 regrafts) averaged over all animals at all time points. T cell proliferation values are normalized to paired untreated control wells. Wells treated with the positive control concanavalin A (ConA) show a response, but no response is evident with cells cultured with replicate graft material or PTFE. IgE blood baseline concentrations showed substantial variance, but no increase in IgE, IgG, or IgM is indicated. Paired symbols (*, $, and #) in the plot indicate P < 0.05. See figs. S7 and S8 for values for each animal at all time points.

Supplementary Materials

  • www.sciencetranslationalmedicine.org/cgi/content/full/9/414/eaan4209/DC1

    Fig. S1. Study design of AVG implantation.

    Fig. S2. Kaplan-Meier diagram comparing graft patency for cephalic (n = 6) versus brachial (n = 5) outflow veins.

    Fig. S3. Plot of graft diameters measured by ultrasound for all grafts contributing to the patency rates (n = 6).

    Fig. S4. Full-size angiogram of all 6-month explants (n = 3).

    Fig. S5. Verhoeff–van Gieson staining of explants.

    Fig. S6. Histological section of graft-vein junction at distal anastomosis of BAVG1.

    Fig. S7. IgE, IgG, and IgM blood concentrations measured for all animals and all time points.

    Fig. S8. T cell proliferation measured for all animals and all time points.

    Table S1. Immunohistochemistry antibodies and conditions.

  • Supplementary Material for:

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

    Zeeshan H. Syedain, Melanie L. Graham, Ty B. Dunn, Timothy O'Brien, Sandra L. Johnson, Robert J. Schumacher, Robert T. Tranquillo*

    *Corresponding author. Email: tranquillo{at}umn.edu

    Published 1 November 2017, Sci. Transl. Med. 9, eaan4209 (2017)
    DOI: 10.1126/scitranslmed.aan4209

    This PDF file includes:

    • Fig. S1. Study design of AVG implantation.
    • Fig. S2. Kaplan-Meier diagram comparing graft patency for cephalic (n = 6) versus brachial (n = 5) outflow veins.
    • Fig. S3. Plot of graft diameters measured by ultrasound for all grafts contributing to the patency rates (n = 6).
    • Fig. S4. Full-size angiogram of all 6-month explants (n = 3).
    • Fig. S5. Verhoeff–van Gieson staining of explants.
    • Fig. S6. Histological section of graft-vein junction at distal anastomosis of BAVG1.
    • Fig. S7. IgE, IgG, and IgM blood concentrations measured for all animals and all time points.
    • Fig. S8. T cell proliferation measured for all animals and all time points.
    • Table S1. Immunohistochemistry antibodies and conditions.

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