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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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Extracellular matrix deposition was evident in TEVG over the course of the 12-month experiment.A. Histologic analysis of graft tissue testing for elastin (EVG: Elastica van Giesen), collagen, elastic and cellular architecture (Movat’s and Masson trichrome) (n = 5 in each group). There is minimal elastin within the graft as compared to that that seen in native aorta. There is presence of endothelial and adventitial cells of the grafts with neo-collagen containing extracellular matrix. B. Expression of extracellular matrix components (n = 5–10 in each group). SMC, a marker of smooth muscle cells. Data were normalized using hypoxanthine-guanine phosphoribosyltransferase (HPRT).
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pone.0120328.g005: Extracellular matrix deposition was evident in TEVG over the course of the 12-month experiment.A. Histologic analysis of graft tissue testing for elastin (EVG: Elastica van Giesen), collagen, elastic and cellular architecture (Movat’s and Masson trichrome) (n = 5 in each group). There is minimal elastin within the graft as compared to that that seen in native aorta. There is presence of endothelial and adventitial cells of the grafts with neo-collagen containing extracellular matrix. B. Expression of extracellular matrix components (n = 5–10 in each group). SMC, a marker of smooth muscle cells. Data were normalized using hypoxanthine-guanine phosphoribosyltransferase (HPRT).

Mentions: Presence of a cellular layer resembling endothelium was seen at our earliest time point, 4 months after implantation. This layer progressively increased in thickness over the course of 12 months, without a concomitant decrease in luminal diameter, indicating cellular ingrowth into the graft rather than neointimal hyperplasia (Figs. 4 & 5A).


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)

Extracellular matrix deposition was evident in TEVG over the course of the 12-month experiment.A. Histologic analysis of graft tissue testing for elastin (EVG: Elastica van Giesen), collagen, elastic and cellular architecture (Movat’s and Masson trichrome) (n = 5 in each group). There is minimal elastin within the graft as compared to that that seen in native aorta. There is presence of endothelial and adventitial cells of the grafts with neo-collagen containing extracellular matrix. B. Expression of extracellular matrix components (n = 5–10 in each group). SMC, a marker of smooth muscle cells. Data were normalized using hypoxanthine-guanine phosphoribosyltransferase (HPRT).
© Copyright Policy
Related In: Results  -  Collection

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

pone.0120328.g005: Extracellular matrix deposition was evident in TEVG over the course of the 12-month experiment.A. Histologic analysis of graft tissue testing for elastin (EVG: Elastica van Giesen), collagen, elastic and cellular architecture (Movat’s and Masson trichrome) (n = 5 in each group). There is minimal elastin within the graft as compared to that that seen in native aorta. There is presence of endothelial and adventitial cells of the grafts with neo-collagen containing extracellular matrix. B. Expression of extracellular matrix components (n = 5–10 in each group). SMC, a marker of smooth muscle cells. Data were normalized using hypoxanthine-guanine phosphoribosyltransferase (HPRT).
Mentions: Presence of a cellular layer resembling endothelium was seen at our earliest time point, 4 months after implantation. This layer progressively increased in thickness over the course of 12 months, without a concomitant decrease in luminal diameter, indicating cellular ingrowth into the graft rather than neointimal hyperplasia (Figs. 4 & 5A).

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