儿茶酚-(胺)表面化学介导的一氧化氮催化释放涂层研究  

Chemical-mediated Nitric Oxide-generating Coatings on Catechol-(Amine)Surface

作　　者：刘苗 谢鑫 周吴一凡 缪婉 涂秋芬[1] 熊开琴[1,2] LIU Miao;XIE Xin;ZHOU Wu-yi-fan;MIAO Wan;TU Qiu-fen;XIONG Kai-qin(Key Laboratory of Advanced Technology of Materials of Education Ministry,School of Materials Science and Engineering,Southwest Jiaotong University,Chengdu 610031,China;State Key Laboratory of Molecular Engineering of Polymers,Fudan University,Shanghai 200438,China)

机构地区：[1]西南交通大学材料科学与工程学院材料先进技术教育部重点实验室,成都610031 [2]复旦大学聚合物分子工程国家重点实验室,上海200438

出　　处：《表面技术》2023年第3期327-337,共11页Surface Technology

基　　金：国家自然科学基金(82072072);南方医科大学附属东莞医院高层次人才支持与发展计划(K202102);四川省国际科技创新合作项目(2021YFH0056)。

摘　　要：目的在316L不锈钢(SS)表面构建原位一氧化氮(NO)催化释放涂层,使其能特异选择性地抗凝血、抑制平滑肌细胞(SMCs)增生,从而促进内皮细胞(ECs)生长。方法在弱碱性水溶液中,选用多巴胺(DA)和己二胺(HD)为前驱体,利用多巴胺邻二苯酚结构自聚合沉膜的能力、多巴胺与己二胺的酚-(胺)表面化学,通过简单的一锅法在316L SS表面构建富氨基粘附涂层DA/HD。再通过碳二亚胺化学交联反应,共价接枝螯合Cu^(2+)的1,4,7,10-四氮杂环十二烷-1,4,7,10-四羧酸(DOTA),最后获得均匀且稳定的NO催化释放涂层(命名为Cu-DOTA@DA/HD)。结果DA/HD涂层表面的氨基密度高达22 nmol/cm^(2),实现了Cu-DOTA的有效固定,其NO催化释放速率可达5.2×10^(-10)mol/(cm^(2)·min)。Cu-DOTA@DA/HD涂层显著地抑制了血小板的粘附和激活,也能有效抑制血栓的形成,其表面血栓总质量由316L SS的(40.3±10.3)mg降低至(3.0±0.4)mg。Cu-DOTA@DA/HD涂层催化释放的NO赋予了316L SS选择性地抑制SMCs粘附和增殖,从而促进了ECs生长的功能。结论基于儿茶酚-(胺)表面化学构建的NO催化涂层,成功地实现了316L SS表面持续、稳定的NO催化释放,赋予了其抗凝血、选择性抑制SMCs增殖和促进EC生长等多重生物学功能,在血液接触类器械(如体外循环导管和血管支架表面)应用方面具有潜在价值。It is an advanced surface technology that can improve the biocompatibility and hemocompatibility of blood contact-like material surfaces by constructing an in situ nitric oxide(NO)catalytic release coating on the surface of 316L stainless steel(SS)without changing the physical properties of the substrate material.The biocompatibility and hemocompatibility of unmodified 316L stainless steel(SS)are too poor to cause complications such as acute thrombosis and smooth muscle cell proliferation after implantation,which can inhibit the regenerative repair of diseased tissue.Thus,in this work,a NO-catalyzed coating based on the chemical construction of catechol-(amine)surface was investigated,and a sustained and stable NO-catalyzed release from the surface of 316L SS was successfully achieved,endowing it with multiple biological functions such as anti-coagulation,selective inhibition of SMCs proliferation and promotion of EC growth.In this work,316L SS disc with 1 cm diameter was used as the study object.First,the samples were cleaned by sonication with acetone and anhydrous ethanol,dried sufficiently and then prepared for use.Subsequently,the samples were immersed in the reaction solution of DA(1 mg/mL)and HD(2.44 mg/mL)dissolved by Tris-base,then the solution reacted at a constant temperature of 37℃ for 24 hours.After the reaction,the DA/HD-coated modified samples were removed and washed thoroughly with distilled water.Subsequently,DOTA(0.01 mg/mL),EDC(0.0066 mg/mL),NHS(0.0033 mg/mL)and MES(0.65 mol/L)were fully dissolved in deionized water and the pH of the solution was adjusted to 5.4.After the reaction at 37℃for 30 min,the appropriate amount of Cu Cl2-2H2O was fully dissolved in the above solution to prepare Cu-DOTA solution with a concentration of 0.003 mg/mL.Finally,1 mL of Cu-DOTA solution was added to the surface of each sample,and after grafting reaction at 25℃ for 24 hours,the samples were removed,then washed with distilled water.Finally,Cu-DOTA@DA/HD coating modified samples were obtained,and a series o

关 键 词：表面化学 一氧化氮 抗凝血 平滑肌细胞 内皮细胞 

分 类 号：R318[医药卫生—生物医学工程]