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载有西罗莫司的丝质微针贴片包裹抑制静脉移植物模型中的内膜增生。

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

机构信息

Division of Cardiovascular Surgery, Department of Thoracic and Cardiovascular Surgery, Severance Cardiovascular Hospital, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.

School of Mechanical Engineering, Yonsei University, Seoul 03722, Republic of Korea.

出版信息

Int J Mol Sci. 2023 Feb 7;24(4):3306. doi: 10.3390/ijms24043306.

DOI:10.3390/ijms24043306
PMID:36834717
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9967879/
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.

摘要

我们研究了载有西罗莫司的丝质微针（MN）套作为外部血管装置在药物输送效果、抑制新生内膜增生和血管重塑方面的作用。使用犬作为模型，建立了静脉移植物模型以将颈动脉或股动脉与颈静脉或股静脉进行吻合。对照组包含 4 只仅吻合移植物的犬；干预组包含 4 只吻合载有西罗莫司的丝质 MN 套的静脉移植物的犬。植入后 12 周，每组取出 15 个静脉移植物进行分析。应用罗丹明 B 嵌入丝质 MN 套的静脉移植物显示出远高于对照组的荧光信号。干预组的静脉移植物直径减小或保持稳定而没有扩张，而对照组则增加。干预组的股静脉移植物的平均新生内膜与中膜比值明显较低，并且其内膜层的胶原密度比值明显低于对照组。总之，载有西罗莫司的丝质 MN 套在静脉移植物模型中成功地将药物输送到静脉移植物的内膜层。它防止了静脉移植物的扩张，避免了剪切力和降低了壁张力，并抑制了新生内膜增生。

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