| KE You,HUANG Nan,XIONG Kaiqin,MA Qing,ZHOU Nan,WU Yu,TU Qiufen.Icariin-eluting Coating Modified Vascular Stent with Lesion Healing Function[J],53(18):219-230 |
| Icariin-eluting Coating Modified Vascular Stent with Lesion Healing Function |
| Received:October 17, 2023 Revised:December 26, 2023 |
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| DOI：10.16490/j.cnki.issn.1001-3660.2024.18.020 |
| KeyWord:icariin drug-eluting coating pro-endothelial anti-inflammatory antithrombosis |
| Author | Institution |
| KE You |
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu , China;Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| HUANG Nan |
Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| XIONG Kaiqin |
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu , China |
| MA Qing |
Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| ZHOU Nan |
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu , China;Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| WU Yu |
Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| TU Qiufen |
Institute of Biomedical Engineering, College of Medicine, Southwest Jiaotong University, Chengdu , China;Key Laboratory of Advanced Technologies of Materials Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
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| Abstract: |
| Cardiovascular disease, as the leading cause of global human disease-related deaths, is one of the most prevalent and deadly health threats worldwide. Percutaneous coronary intervention with the implantation of cardiovascular stents is considered one of the most effective treatment methods. Stents act as mechanical support, providing structural support to maintain the normal patency of blood vessels. However, currently used stents still face issues such as intrastent thrombosis and restenosis. Drug-eluting stents (DES) loaded with drugs like paclitaxel and rapamycin have reduced the risk of restenosis to some extent but may induce de novo atherosclerosis and late stent thrombosis. These anti-tumor drugs can inhibit the proliferation of smooth muscle cells but inevitably hinder the repair and healing of vascular endothelial cells. Therefore, the ideal vascular stent should not only inhibit abnormal smooth muscle cell proliferation but also possess anti-inflammatory, anti-thrombotic, and endothelial-promoting functions. Icariin (ICA) is a flavonoid compound extracted from the Epimedium plant, known for its various biological functions, including antioxidant, anti-inflammatory, antimicrobial, and anti-tumor properties. In this study, an icariin drug-eluting coating with lesion healing capabilities was constructed on the surface of vascular stents with the ultrasonic atomization spray technology. With PLGA as a drug delivery system carrier, it not only exhibited good biocompatibility but also preserved the activity of ICA, enabling targeted drug delivery and increasing treatment precision. This coating enhanced the biocompatibility of the material surface without altering the base material. The study involved the preparation of drug-eluting coatings on 316L SS stainless steel specimens (1 cm × 1 cm) and medical-grade 316L SS vascular stents. In a 2 mg/mL PLGA solution (solvent:tetrahydrofuran), different proportions of icariin (0%, 10%, 20%, 30%, 40% by mass) were added. Drug-loaded PLGA coatings were then fabricated onto the substrates by evaporative deposition or ultrasound atomization spraying techniques. The ultrasound atomization system operated at 2 W of ultrasound power, with a solution flow rate of 0.75 cm/sec, and a total of 40 deposition cycles. The chemical composition of the coatings was analyzed by Fourier-transform infrared spectroscopy (FTIR), while the wettability of the samples was determined through a water contact angle (WCA) measurement. The microstructure of the coatings on the vascular stents was observed by scanning electron microscopy (SEM). The drug release behavior of the coatings was assessed by UV-Vis spectrophotometry. In vitro experiments were conducted to evaluate the blood compatibility of the coatings, including hemolysis rate and platelet adhesion and activation. Additionally, in vitro cell experiments were performed to assess the influence of the drug-eluting coatings on endothelial cells, smooth muscle cells, and macrophage proliferation. Immunofluorescence staining was employed to evaluate the effects of icariin-eluting coatings on the adhesion and phenotype of endothelial cells, smooth muscle cells, and macrophages. The results from FTIR, WCA, and SEM confirmed the successful preparation of icariin-eluting coatings. These coatings exhibited sustained drug release in vitro for at least 28 days. Blood compatibility assessments demonstrated that the coatings met the hemolysis rate requirements for biomedical implants and exhibited a significant inhibitory effect on platelet adhesion and aggregation. In vitro cell compatibility results indicated that icariin-eluting coatings promoted the adhesion and proliferation of endothelial cells, suppressed smooth muscle cell proliferation, and effectively regulated macrophage inflammation. Based on the in vitro biocompatibility results, the optimal preparation parameter was determined to be an icariin content of 30%. In summary, the icariin-eluting stent developed in this study achieve long-term and stable icariin release, accompanied by properties such as anti-thrombotic, anti-inflammatory, endothelial promotion, and inhibition of smooth muscle cell abnormal proliferation. This stent hold the potential to offer a safe and effective therapeutic option for patients with cardiovascular diseases. |
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