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Development of small diameter nanofiber tissue engineered arterial grafts.

Kurobe H, Maxfield MW, Tara S, Rocco KA, Bagi PS, Yi T, Udelsman B, Zhuang ZW, Cleary M, Iwakiri Y, Breuer CK, Shinoka T - PLoS ONE (2015)

Bottom Line: TEVG group showed significant increases in expressions of SMC marker, collagen-I and III, matrix metalloproteinases-2 and 9, and itgam (a macrophage marker), when compared to sham group.Overall, patency rates were excellent at 12 months after implantation, as structural integrity of these TEVG.Tissue analysis also demonstrated vessel remodeling by autologous cell.

View Article: PubMed Central - PubMed

Affiliation: Nationwide Children's Hospital, Columbus, Ohio, United States of America.

ABSTRACT
The surgical repair of heart and vascular disease often requires implanting synthetic grafts. While synthetic grafts have been successfully used for medium-to-large sized arteries, applications for small diameter arteries (<6 mm) is limited due to high rates of occlusion by thrombosis. Our objective was to develop a tissue engineered vascular graft (TEVG) for small diameter arteries. TEVGs composed of polylactic acid nanofibers with inner luminal diameter between 0.5 and 0.6 mm were surgically implanted as infra-renal aortic interposition conduits in 25 female C17SCID/bg mice. Twelve mice were given sham operations. Survival of mice with TEVG grafts was 91.6% at 12 months post-implantation (sham group: 83.3%). No instances of graft stenosis or aneurysmal dilatation were observed over 12 months post-implantation, assessed by Doppler ultrasound and microCT. Histologic analysis of explanted TEVG grafts showed presence of CD31-positive endothelial monolayer and F4/80-positive macrophages after 4, 8, and 12 months in vivo. Cells positive for α-smooth muscle actin were observed within TEVG, demonstrating presence of smooth muscle cells (SMCs). Neo-extracellular matrix consisting mostly of collagen types I and III were observed at 12 months post-implantation. PCR analysis supports histological observations. TEVG group showed significant increases in expressions of SMC marker, collagen-I and III, matrix metalloproteinases-2 and 9, and itgam (a macrophage marker), when compared to sham group. Overall, patency rates were excellent at 12 months after implantation, as structural integrity of these TEVG. Tissue analysis also demonstrated vessel remodeling by autologous cell.

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Luminal patency and laminar flow were similar between TEVG and native aorta over the course of the 12 month experiment.A. Doppler ultrasound examinations were performed on tissue engineered vascular grafts from 2 weeks to 12 months after implantation. Doppler signals proximal to the graft, distal, and within the graft showed propagation of systemic arterial impulse through the graft. B.In vivo microCTs were performed at 4, 8, and 12 months. Using image analysis software, luminal volume measurements were recorded and then standardized to a 3mm segment. C. & D. When compared to native Aorta in mice having undergone sham operation, there was no significant difference in luminal diameter between both groups and in ratio of TEVG to native aorta at any of the time points.
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pone.0120328.g002: Luminal patency and laminar flow were similar between TEVG and native aorta over the course of the 12 month experiment.A. Doppler ultrasound examinations were performed on tissue engineered vascular grafts from 2 weeks to 12 months after implantation. Doppler signals proximal to the graft, distal, and within the graft showed propagation of systemic arterial impulse through the graft. B.In vivo microCTs were performed at 4, 8, and 12 months. Using image analysis software, luminal volume measurements were recorded and then standardized to a 3mm segment. C. & D. When compared to native Aorta in mice having undergone sham operation, there was no significant difference in luminal diameter between both groups and in ratio of TEVG to native aorta at any of the time points.

Mentions: Implanted TEVGs were serially monitored by ultrasound to assess changes in both graft patency and diameter for up to 12 months (Fig. 2A, B). Average luminal diameter was 0.46 ± 0.04 mm at 3 days (n = 25), 0.45 ± 0.03 mm at 1 weeks (n = 24), 0.46 ± 0.02 mm at 2 weeks (n = 10), 0.47 ± 0.05 mm at 1 months (n = 15), 0.46 ± 0.04 mm at 2 months (n = 8), 0.47 ± 0.03 mm at 4 months (n = 21), 0.46 ± 0.03 at 6 months (n = 12), 0.47 ± 0.03 at 8 months (n = 16), 0.46 ± 0.02 at 10 months (n = 6), and 0.47 ± 0.01 at 12 months (n = 8) (Fig. 2C).


Development of small diameter nanofiber tissue engineered arterial grafts.

Kurobe H, Maxfield MW, Tara S, Rocco KA, Bagi PS, Yi T, Udelsman B, Zhuang ZW, Cleary M, Iwakiri Y, Breuer CK, Shinoka T - PLoS ONE (2015)

Luminal patency and laminar flow were similar between TEVG and native aorta over the course of the 12 month experiment.A. Doppler ultrasound examinations were performed on tissue engineered vascular grafts from 2 weeks to 12 months after implantation. Doppler signals proximal to the graft, distal, and within the graft showed propagation of systemic arterial impulse through the graft. B.In vivo microCTs were performed at 4, 8, and 12 months. Using image analysis software, luminal volume measurements were recorded and then standardized to a 3mm segment. C. & D. When compared to native Aorta in mice having undergone sham operation, there was no significant difference in luminal diameter between both groups and in ratio of TEVG to native aorta at any of the time points.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4382213&req=5

pone.0120328.g002: Luminal patency and laminar flow were similar between TEVG and native aorta over the course of the 12 month experiment.A. Doppler ultrasound examinations were performed on tissue engineered vascular grafts from 2 weeks to 12 months after implantation. Doppler signals proximal to the graft, distal, and within the graft showed propagation of systemic arterial impulse through the graft. B.In vivo microCTs were performed at 4, 8, and 12 months. Using image analysis software, luminal volume measurements were recorded and then standardized to a 3mm segment. C. & D. When compared to native Aorta in mice having undergone sham operation, there was no significant difference in luminal diameter between both groups and in ratio of TEVG to native aorta at any of the time points.
Mentions: Implanted TEVGs were serially monitored by ultrasound to assess changes in both graft patency and diameter for up to 12 months (Fig. 2A, B). Average luminal diameter was 0.46 ± 0.04 mm at 3 days (n = 25), 0.45 ± 0.03 mm at 1 weeks (n = 24), 0.46 ± 0.02 mm at 2 weeks (n = 10), 0.47 ± 0.05 mm at 1 months (n = 15), 0.46 ± 0.04 mm at 2 months (n = 8), 0.47 ± 0.03 mm at 4 months (n = 21), 0.46 ± 0.03 at 6 months (n = 12), 0.47 ± 0.03 at 8 months (n = 16), 0.46 ± 0.02 at 10 months (n = 6), and 0.47 ± 0.01 at 12 months (n = 8) (Fig. 2C).

Bottom Line: TEVG group showed significant increases in expressions of SMC marker, collagen-I and III, matrix metalloproteinases-2 and 9, and itgam (a macrophage marker), when compared to sham group.Overall, patency rates were excellent at 12 months after implantation, as structural integrity of these TEVG.Tissue analysis also demonstrated vessel remodeling by autologous cell.

View Article: PubMed Central - PubMed

Affiliation: Nationwide Children's Hospital, Columbus, Ohio, United States of America.

ABSTRACT
The surgical repair of heart and vascular disease often requires implanting synthetic grafts. While synthetic grafts have been successfully used for medium-to-large sized arteries, applications for small diameter arteries (<6 mm) is limited due to high rates of occlusion by thrombosis. Our objective was to develop a tissue engineered vascular graft (TEVG) for small diameter arteries. TEVGs composed of polylactic acid nanofibers with inner luminal diameter between 0.5 and 0.6 mm were surgically implanted as infra-renal aortic interposition conduits in 25 female C17SCID/bg mice. Twelve mice were given sham operations. Survival of mice with TEVG grafts was 91.6% at 12 months post-implantation (sham group: 83.3%). No instances of graft stenosis or aneurysmal dilatation were observed over 12 months post-implantation, assessed by Doppler ultrasound and microCT. Histologic analysis of explanted TEVG grafts showed presence of CD31-positive endothelial monolayer and F4/80-positive macrophages after 4, 8, and 12 months in vivo. Cells positive for α-smooth muscle actin were observed within TEVG, demonstrating presence of smooth muscle cells (SMCs). Neo-extracellular matrix consisting mostly of collagen types I and III were observed at 12 months post-implantation. PCR analysis supports histological observations. TEVG group showed significant increases in expressions of SMC marker, collagen-I and III, matrix metalloproteinases-2 and 9, and itgam (a macrophage marker), when compared to sham group. Overall, patency rates were excellent at 12 months after implantation, as structural integrity of these TEVG. Tissue analysis also demonstrated vessel remodeling by autologous cell.

Show MeSH
Related in: MedlinePlus