Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model

We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugul...

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Main Authors: Jung-Hwan Kim, Eui Hwa Jang, Ji-Yeon Ryu, Jiyong Lee, Jae Ho Kim, Wonhyoung Ryu, Young-Nam Youn
Format: Article
Language:English
Published: MDPI AG 2023-02-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/24/4/3306
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author Jung-Hwan Kim
Eui Hwa Jang
Ji-Yeon Ryu
Jiyong Lee
Jae Ho Kim
Wonhyoung Ryu
Young-Nam Youn
author_facet Jung-Hwan Kim
Eui Hwa Jang
Ji-Yeon Ryu
Jiyong Lee
Jae Ho Kim
Wonhyoung Ryu
Young-Nam Youn
author_sort Jung-Hwan Kim
collection DOAJ
description We investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B–embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.
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spelling doaj.art-b8b3f4a7f01c41c99934cf257d4d83f52023-11-16T20:58:08ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01244330610.3390/ijms24043306Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft ModelJung-Hwan Kim0Eui Hwa Jang1Ji-Yeon Ryu2Jiyong Lee3Jae Ho Kim4Wonhyoung Ryu5Young-Nam Youn6Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDivision of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaDivision of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaSchool of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of KoreaSchool of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of KoreaSchool of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of KoreaDivision of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of KoreaWe investigated the role of a sirolimus-embedded silk microneedle (MN) wrap as an external vascular device for drug delivery efficacy, inhibition of neointimal hyperplasia, and vascular remodeling. Using dogs, a vein graft model was developed to interpose the carotid or femoral artery with the jugular or femoral vein. The control group contained four dogs with only interposed grafts; the intervention group contained four dogs with vein grafts in which sirolimus-embedded silk-MN wraps were applied. After 12-weeks post-implantation, 15 vein grafts in each group were explanted and analyzed. Vein grafts applied with the rhodamine B–embedded silk-MN wrap showed far higher fluorescent signals than those without the wrap. The diameter of vein grafts in the intervention group decreased or remained stable without dilatation; however, it increased in the control group. The intervention group had femoral vein grafts with a significantly lower mean neointima-to-media ratio, and had vein grafts with an intima layer showing a significantly lower collagen density ratio than the control group. In conclusion, sirolimus-embedded silk-MN wrap in a vein graft model successfully delivered the drug to the intimal layer of the vein grafts. It prevented vein graft dilatation, avoiding shear stress and decreasing wall tension, and it inhibited neointimal hyperplasia.https://www.mdpi.com/1422-0067/24/4/3306neointimal hyperplasiavein graftmicroneedlesilk fibroinperivascular drug deliveryvascular wraps
spellingShingle Jung-Hwan Kim
Eui Hwa Jang
Ji-Yeon Ryu
Jiyong Lee
Jae Ho Kim
Wonhyoung Ryu
Young-Nam Youn
Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
International Journal of Molecular Sciences
neointimal hyperplasia
vein graft
microneedle
silk fibroin
perivascular drug delivery
vascular wraps
title Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
title_full Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
title_fullStr Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
title_full_unstemmed Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
title_short Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
title_sort sirolimus embedded silk microneedle wrap to prevent neointimal hyperplasia in vein graft model
topic neointimal hyperplasia
vein graft
microneedle
silk fibroin
perivascular drug delivery
vascular wraps
url https://www.mdpi.com/1422-0067/24/4/3306
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