| YANG Mengyi,HUANG Nan,XIONG Kaiqin,DU Zeyu,MA Qing,XU Jiale,WANG Chuanzhe,TU Qiufen.Pro-endothelial and Anti-inflammatory Tanshinone IIA-Eluting Stent Coating[J],53(6):222-233 |
| Pro-endothelial and Anti-inflammatory Tanshinone IIA-Eluting Stent Coating |
| Received:March 17, 2023 Revised:May 05, 2023 |
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| DOI：10.16490/j.cnki.issn.1001-3660.2024.06.021 |
| KeyWord:tanshinone IIA drug-eluting stent pro-endothelial anti-inflammatory anti-thrombosis vascular cytocompatibility |
| Author | Institution |
| YANG Mengyi |
Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| HUANG Nan |
Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| XIONG Kaiqin |
Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| DU Zeyu |
Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| MA Qing |
Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| XU Jiale |
Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| WANG Chuanzhe |
Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
| TU Qiufen |
Key Laboratory of Advanced Materials Technology of Ministry of Education, School of Materials Science and Engineering, Southwest Jiaotong University, Chengdu , China |
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| Abstract: |
| Cardiovascular disease is one of the most common causes of death worldwide and is widely recognized as the leading killer of human health. Cardiovascular stent intervention is currently the primary treatment for cardiovascular disease. The most widely used drug-eluting stents (DES) reduce the incidence of restenosis to approximately 3%-20% based on bare metal stents (BMS), but the released drugs inhibit endothelial proliferation while impairing the function of the endothelial layer, causing a series of cellular dysfunctional events such as thrombosis, abnormal proliferation of smooth muscle cells (SMCs), inflammatory response, delayed re-endothelialisation and even the development of advanced neoatherosclerosis. To address these issues, an ideal vascular stent should have multiple biological functions such as promoting the proliferation of endothelial cells (ECs), inhibiting the overproliferation of SMCs, regulating inflammation and being antithrombotic. Tanshinone IIA (TS) is one of the most pharmacologically active components isolated from the traditional Chinese medicine Salvia miltiorrhiza, which has anti-atherosclerotic, anti-inflammatory, antioxidant and anti-thrombotic effects. In order to maintain the active structure of TS during application, TS-eluting stents were prepared by ultrasonic atomisation spraying and its therapeutic effects in atherosclerotic site were explored. A coating carrier, polylactic acid-hydroxyacetic acid copolymer (PLGA), which had excellent physical strength, controlled degradation properties and the ability to contain large amounts of drug without altering the degradation pattern was selected. Water contact angle (WCA) detector and Fourier transform infrared absorption spectrometer (FTIR) were selected to examine the hydrophobicity, chemical composition and structure of the coating surface, and the mechanical properties of the coating on the stent surface were evaluated by means of balloon expansion experiments and field emission scanning electron microscopy (SEM) observations. The drug release behavior of the coating was examined by an UV-Vis spectrophotometer. The haemocompatibility of the coating was initially evaluated by in vitro haemolysis rate and platelet adhesion and activation assays. The effects of the TS coating on the proliferation of endothelial cells (ECs) and smooth muscle cells (SMCs) and the modulation of macrophage inflammatory function were assessed by in vitro cellular assays. The modulatory effect of the TS coating on macrophage phenotype was assessed using immunofluorescence staining. The antithrombotic effect of the coating was further explored by ex-vivo blood circulation assays. The successful preparation of TS-eluting stent was confirmed by WCA, FTIR, SEM and UV-Vis assays. The TS coating was able to maintain sustained release of TS in vitro for 28 d. The TS coating met the haemolysis rate requirement for biomedical implant materials. The in vitro cytocompatibility results showed that the TS eluting coating promoted the proliferation of ECs and inhibited the proliferation of SMCs, and could effectively regulate the inflammatory behavior of macrophages. Based on the in vitro biocompatibility results, a final concentration of 30% TS (mass ratio of TS to PLGA) was selected as the final application concentration. The results of the ex-vivo blood circulation experiments showed that the surface coating had a good inhibitory effect on thrombosis. In conclusion, the TS-eluting stent prepared herein has the ability to selectively promote endothelial proliferation, inhibit smooth muscle proliferation, modulate inflammation as well as excellent anti-thrombogenic ability, which can provide a potential solution for lesion vascular repair. |
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