他克莫司洗脱支架在猪冠状动脉模型中的疗效和安全性评估。

Efficacy and Safety Evaluation of Tacrolimus-Eluting Stent in a Porcine Coronary Artery Model.

机构信息

The Korea Cardiovascular Stent Research Institute, Chonnam National University, Gwangju, Korea.

The Cardiovascular Convergence Research Center of Chonnam National University Hospital Designated by Korea Ministry of Health and Welfare, Gwangju, Korea.

出版信息

Tissue Eng Regen Med. 2024 Jul;21(5):723-735. doi: 10.1007/s13770-024-00646-0. Epub 2024 Jun 4.

DOI:10.1007/s13770-024-00646-0

PMID:38834902

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11187055/

Abstract

BACKGROUND

A drug-eluting stent (DES) is a highly beneficial medical device used to widen or unblock narrowed blood vessels. However, the drugs released by the implantation of DES may hinder the re-endothelialization process, increasing the risk of late thrombosis. We have developed a tacrolimus-eluting stent (TES) that as acts as a potent antiproliferative and immunosuppressive agent, enhancing endothelial regeneration. In addition, we assessed the safety and efficacy of TES through both in vitro and in vivo tests.

METHODS

Tacrolimus and Poly(lactic-co-glycolic acid) (PLGA) were applied to the metal stent using electrospinning equipment. The surface morphology of the stent was examined before and after coating using a scanning electron microscope (SEM) and energy dispersive X-rays (EDX). The drug release test was conducted through high-performance liquid chromatography (HPLC). Cell proliferation and migration assays were performed using smooth muscle cells (SMC). The stent was then inserted into the porcine coronary artery and monitored for a duration of 4 weeks.

RESULTS

SEM analysis confirmed that the coating surface was uniform. Furthermore, EDX analysis showed that the surface was coated with both polymer and drug components. The HPCL analysis of TCL at a wavelength of 215 nm revealed that the drug was continuously released over a period of 4 weeks. Smooth muscle cell migration was significantly decreased in the tacrolimus group (54.1% ± 11.90%) compared to the non-treated group (90.1% ± 4.86%). In animal experiments, the stenosis rate was significantly reduced in the TES group (29.6% ± 7.93%) compared to the bare metal stent group (41.3% ± 10.18%). Additionally, the fibrin score was found to be lower in the TES group compared to the group treated with a sirolimus-eluting stent (SES).

CONCLUSION

Similar to SES, TES reduces neointimal proliferation in a porcine coronary artery model, specifically decreasing the fibrins score. Therefore, tacrolimus could be considered a promising drug for reducing restenosis and thrombosis.

摘要

背景

药物洗脱支架（DES）是一种非常有益的医疗器械，用于拓宽或疏通狭窄的血管。然而，DES 植入后释放的药物可能会阻碍再内皮化过程，增加迟发性血栓形成的风险。我们开发了一种他克莫司洗脱支架（TES），它作为一种有效的抗增殖和免疫抑制药物，增强内皮细胞再生。此外，我们通过体外和体内试验评估了 TES 的安全性和有效性。

方法

采用静电纺丝设备将他克莫司和聚乳酸-羟基乙酸共聚物（PLGA）涂覆在金属支架上。用扫描电子显微镜（SEM）和能谱仪（EDX）观察支架涂覆前后的表面形态。采用高效液相色谱法（HPLC）进行药物释放试验。用平滑肌细胞（SMC）进行细胞增殖和迁移试验。然后将支架插入猪冠状动脉，并监测 4 周。

结果

SEM 分析证实涂层表面均匀。此外，EDX 分析表明表面涂有聚合物和药物成分。在波长为 215nm 的 TCL 的 HPCL 分析表明，药物在 4 周内持续释放。与未处理组（90.1%±4.86%）相比，他克莫司组（54.1%±11.90%）平滑肌细胞迁移明显减少。动物实验中，TES 组（29.6%±7.93%）狭窄率明显低于裸金属支架组（41.3%±10.18%）。此外，与西罗莫司洗脱支架（SES）治疗组相比，TES 组的纤维蛋白评分较低。