Bioengineered vascular access maintains structural integrity in response to arteriovenous flow and repeated needle puncture Bryan W. Tillman, MD, PhD,

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Presentation transcript:

Bioengineered vascular access maintains structural integrity in response to arteriovenous flow and repeated needle puncture Bryan W. Tillman, MD, PhD, Saami K. Yazdani, PhD, Lucas P. Neff, MD, Matthew A. Corriere, MD, MSc, George J. Christ, PhD, Shay Soker, PhD, Anthony Atala, MD, Randolph L. Geary, MD, James J. Yoo, MD, PhD Journal of Vascular Surgery Volume 56, Issue 3, Pages 783-793 (September 2012) DOI: 10.1016/j.jvs.2012.02.030 Copyright © 2012 Society for Vascular Surgery Terms and Conditions

Fig 1 Preimplant specimens and operative images. Images of lyophilized decellularized scaffold (A) and a preimplant endothelial cell (EC)-lined scaffold stained with the nuclear stain DAPI, which demonstrates an endothelial monolayer present on the scaffold lumen at the time of implant (B). Operative photograph of bioengineered graft (C) placement in a loop configuration between carotid artery (CA) and jugular vein (JV) overlying the sternocleidomastoid muscle (SCM). Side view image of mature arteriovenous (AV) graft at 2 months postimplantation depicting the visible subcutaneous graft and dilated proximal vein (D). Journal of Vascular Surgery 2012 56, 783-793DOI: (10.1016/j.jvs.2012.02.030) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

Fig 2 Angiographic evaluation of tissue-engineered blood vessel (TEBV) grafts. Representative anterior-to-posterior views of grafts using computed tomography angiography (A and B) illustrate stable TEBV wall geometry at 2 and 6 months. However, a typical stenosis is evident at the distal anastomosis of the late graft on computed tomography angiography (B) and digital subtraction fluoroscopy (C). The digital subtraction fluoroscopy image also shows a jet of contrast through the stenosis with adjacent vein wall dilation (C). Arrows mark the distal anastomosis of each graft. Journal of Vascular Surgery 2012 56, 783-793DOI: (10.1016/j.jvs.2012.02.030) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

Fig 3 Flow patterns and graft geometry of engineered vessels. Compared with traditional triphasic flow of the common carotid artery (A), tissue-engineered blood vessel (TEBV) grafts exhibit traditional turbulent flow pattern by pulsed-wave Doppler of the arteriovenous (AV) midgraft (B) as well as by color flow of the loop-configured graft (C). Graft geometry (D) was assessed by ultrasound measurements monthly illustrating only minimal increase in diameter, averaging <6% increase over the 6-month study (E). *At 150 days, one data point was missing despite patency of two grafts. Journal of Vascular Surgery 2012 56, 783-793DOI: (10.1016/j.jvs.2012.02.030) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

Fig 4 Histologic evaluation of endothelial monolayer on explanted specimens. Hematoxylin and eosin histology (400X) revealed an intact endothelial monolayer on several 2-month (A) and projected 6-month (B) explant midgraft specimens. At 2 months, scanning electron microscopy (500X) (C) reveals endothelial confluency on a representative midgraft section. Scale bar shown is 50 μM. Journal of Vascular Surgery 2012 56, 783-793DOI: (10.1016/j.jvs.2012.02.030) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

Fig 5 Evaluation of intimal hyperplasia at distal graft anastomoses. Compared with the absence of intimal thickening observed between the internal elastic lamina and the lumen in both native artery (A) and midgraft section (B) stained with Verhoeff van Giesen (VVG), sections from the distal venous anastomosis reveal marked intimal thickening (C). All images are shown at 100× magnification with a scale bar of 200 μM. Journal of Vascular Surgery 2012 56, 783-793DOI: (10.1016/j.jvs.2012.02.030) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

Fig 6 Histologic evaluation of explant midgraft sections. As illustrated at a magnification of 100X, compared with native artery (A) stained with hematoxylin and eosin, a representative preimplant graft (B) reveals only an endothelial monolayer on the luminal side of the internal elastic lamina (arrow) compared with increased medial cellularity noted by 6 months (C). Verhoeff van Giesen (VVG) staining reveals intact elastin layers in native artery (D), preimplant graft (E), and 6-month explant (F). The scale bar is 200 μM. Journal of Vascular Surgery 2012 56, 783-793DOI: (10.1016/j.jvs.2012.02.030) Copyright © 2012 Society for Vascular Surgery Terms and Conditions

Fig 7 Needlestick histology at 100× magnification reveals collagen deposition at healed needlestick sites. Acute needlestick sites (A-C) were differentiated from healed needlestick sites by expected findings of adherent thrombus (arrow). Compared with hematoxylin and eosin stain of a acute (A-C) and healed needlestick (D-F), there are similar degrees of cellularity at needlesticks (A and D), but a void of collagen is noted in acute needlestick (C) as compared with collagen deposition in the healed needlestick (F). B and E illustrate defects in Verhoeff van Giesen (VVG)-stained sections used to identify needlestick sites as disruption of elastin layers. The scale bar is 200 μM. Journal of Vascular Surgery 2012 56, 783-793DOI: (10.1016/j.jvs.2012.02.030) Copyright © 2012 Society for Vascular Surgery Terms and Conditions