Sirolimus-Embedded Silk Microneedle Wrap to Prevent Neointimal Hyperplasia in Vein Graft Model
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Published:2023-02-07
Issue:4
Volume:24
Page:3306
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ISSN:1422-0067
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Container-title:International Journal of Molecular Sciences
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language:en
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Short-container-title:IJMS
Author:
Kim Jung-Hwan1ORCID,
Jang Eui Hwa1,
Ryu Ji-Yeon1,
Lee Jiyong2,
Kim Jae Ho2ORCID,
Ryu Wonhyoung2ORCID,
Youn Young-Nam1ORCID
Affiliation:
1. Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea
2. School of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of Korea
Abstract
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.
Funder
Ministry of Health & Welfare
Yonsei University College of Medicine
Subject
Inorganic Chemistry,Organic Chemistry,Physical and Theoretical Chemistry,Computer Science Applications,Spectroscopy,Molecular Biology,General Medicine,Catalysis
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