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血管平滑肌细胞和血小板对作为支架涂层材料的表没食子儿茶素没食子酸酯释放型聚(L-丙交酯-共-ε-己内酯)的反应。

The behavior of vascular smooth muscle cells and platelets onto epigallocatechin gallate-releasing poly(l-lactide-co-epsilon-caprolactone) as stent-coating materials.

作者信息

Cho Han Hee, Han Dong-Wook, Matsumura Kazuaki, Tsutsumi Sadami, Hyon Suong-Hyu

机构信息

Department of Medical Simulation Engineering, Research Center for Nano Medical Engineering, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.

出版信息

Biomaterials. 2008 Mar;29(7):884-93. doi: 10.1016/j.biomaterials.2007.10.052. Epub 2007 Nov 26.

Abstract

Localized drug delivery from drug-eluting stents has been accepted as one of the most promising treatment methods for preventing restenosis after stenting. However, thrombosis, inflammation, and restenosis are still major problems for the utility of cardiovascular prostheses such as vascular grafts and stents. Epigallocatechin-3-O-gallate (EGCG), a major polyphenolic constituent of green tea, has been shown to have anti-thrombotic, anti-inflammatory and anti-proliferative activities. It was hypothesized that controlled release of EGCG from biodegradable poly(lactide-co-epsilon-caprolactone, PLCL) stent coatings would suppress migration and invasion of vascular smooth muscle cells (VSMCs) as well as platelet-mediated thrombosis. EGCG-releasing PLCL (E-PLCL) was prepared by blending PLCL with 5% EGCG. The surface morphology, roughness and melting temperature of PLCL were not changed despite EGCG addition. EGCG did, however, EGCG appreciably increase the hydrophilicity of PLCL. EGCG was found to be uniformly dispersed throughout E-PLCL without direct chemical interactions with PLCL. E-PLCL displayed diffusion controlled release of EGCG release for periods up to 34 days. E-PLCL significantly suppressed the migration and invasion of VSMCs as well as the adhesion and activation of platelets. E-PLCL coatings were able to smooth the surface of bare stents with neither cracks nor webbings after balloon expansion. The structural integrity of coatings was sufficient to resist delamination or destruction during 90% dilatation. These results suggest that EGCG-releasing polymers can be effectively applied for fabricating an EGCG-eluting vascular stent to prevent in-stent restenosis and thrombosis.

摘要

药物洗脱支架的局部药物递送已被公认为是预防支架置入术后再狭窄最有前景的治疗方法之一。然而,血栓形成、炎症和再狭窄仍然是诸如血管移植物和支架等心血管假体应用中的主要问题。表没食子儿茶素-3-O-没食子酸酯(EGCG)是绿茶中的一种主要多酚成分,已被证明具有抗血栓、抗炎和抗增殖活性。据推测,从可生物降解的聚(丙交酯-共-ε-己内酯,PLCL)支架涂层中控制释放EGCG将抑制血管平滑肌细胞(VSMC)的迁移和侵袭以及血小板介导的血栓形成。通过将PLCL与5%的EGCG混合制备了释放EGCG的PLCL(E-PLCL)。尽管添加了EGCG,但PLCL的表面形态、粗糙度和熔点并未改变。然而,EGCG确实显著增加了PLCL的亲水性。发现EGCG均匀地分散在整个E-PLCL中,与PLCL没有直接的化学相互作用。E-PLCL在长达34天的时间内显示出EGCG的扩散控制释放。E-PLCL显著抑制了VSMC的迁移和侵袭以及血小板的粘附和活化。E-PLCL涂层能够在球囊扩张后使裸支架表面光滑,没有裂缝或网状物。涂层的结构完整性足以抵抗90%扩张过程中的分层或破坏。这些结果表明,释放EGCG的聚合物可有效地应用于制造EGCG洗脱血管支架,以预防支架内再狭窄和血栓形成。

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