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通过氢化非晶碳薄膜对 2-甲基丙烯酰氧乙基磷酸胆碱聚合物表面进行微图案化处理,以实现内皮细胞化和抗血栓形成。

Micropatterning of a 2-methacryloyloxyethyl phosphorylcholine polymer surface by hydrogenated amorphous carbon thin films for endothelialization and antithrombogenicity.

机构信息

Department of Mechanical Engineering, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.

Department of Mechanical Engineering, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan; Department of Radiology, Tokai University Hachioji Hospital, Tokai University School of Medicine, 1838 Ishikawa-cho, Hachioji-shi, Tokyo 192-0032, Japan.

出版信息

Acta Biomater. 2019 Mar 15;87:187-196. doi: 10.1016/j.actbio.2019.01.059. Epub 2019 Jan 31.

Abstract

The existing first-generation drug-eluting stent (DES) has caused late and very late stent thrombosis related to incomplete stent endothelialization. Hence, biomaterials that possess sufficient anti-thrombogenicity and endothelialization with the controlled drug release system have been highly required. In this work, we have developed a newly designed drug-release platform composed of 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, a non-thrombogenic polymer, and micropatterned hydrogenated amorphous carbon (a-C:H), a cell-compatible thin film. The platelet adhesion and the endothelial cell adhesion behavior on the micropatterned substrates were investigated in vitro. The results indicated that the micropatterned a-C:H/MPC polymer substrates effectively supported the human umbilical vein endothelial cell (HUVEC) proliferation, while suppressing the platelet adhesion. Interestingly, the HUVEC exhibited different shape and behavior by changing the island size of the micropatterned a-C:H. By introducing both a non-thrombogenic polymer and cell-compatible thin films through a simple patterning method, we demonstrated that the platform had the potential to be utilized as a base material for DES with cell controllability. STATEMENT OF SIGNIFICANCE: The current first-generation drug-eluting stents (DES) would cause late and very late stent thrombosis due to the incomplete endothelialization of the metal stent material. In this work, we have developed a new DES platform composed of a 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer micropatterned by hydrogenated amorphous carbon (a-C:H). Two types of differently micropatterned a-C:H stent surface were made. Our studies revealed that the micropatterned a-C:H/MPC polymer substrates could effectively enhance the endothelial cell (EC) proliferation, simultaneously suppressing the platelet adhesion, becoming a highly biocompatible material especially for indwelling devices including a drug-release device. The new drug-release platform could be utilized as a base material for cell-controllable coating on DES.

摘要

现有的第一代药物洗脱支架(DES)由于金属支架材料的内皮化不完全,会导致晚期和极晚期支架内血栓形成。因此,人们迫切需要具有足够抗血栓形成和内皮化能力的生物材料,并能控制药物释放系统。在这项工作中,我们开发了一种由 2-(甲基丙烯酰氧)乙基磷酸胆碱(MPC)聚合物和微图案化氢化非晶碳(a-C:H)组成的新型药物释放平台,后者是一种细胞相容的薄膜。体外研究了血小板黏附和内皮细胞在微图案化基底上的黏附行为。结果表明,微图案化的 a-C:H/MPC 聚合物基底有效地支持了人脐静脉内皮细胞(HUVEC)的增殖,同时抑制了血小板黏附。有趣的是,通过改变微图案化 a-C:H 的岛尺寸,HUVEC 表现出不同的形状和行为。通过简单的图案化方法引入非血栓形成聚合物和细胞相容薄膜,我们证明了该平台有可能作为具有细胞可控性的 DES 的基础材料。

意义声明

当前的第一代药物洗脱支架(DES)由于金属支架材料的内皮化不完全,会导致晚期和极晚期支架内血栓形成。在这项工作中,我们开发了一种由 2-(甲基丙烯酰氧)乙基磷酸胆碱(MPC)聚合物和微图案化氢化非晶碳(a-C:H)组成的新型 DES 平台。两种不同图案化的 a-C:H 支架表面被制作出来。我们的研究表明,微图案化的 a-C:H/MPC 聚合物基底可以有效地增强内皮细胞(EC)的增殖,同时抑制血小板黏附,成为一种高度生物相容的材料,特别是对于包括药物释放装置在内的留置装置。这种新的药物释放平台可以作为细胞可控涂层在 DES 上的基础材料。

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