TiO2纳米管/羟基磷灰石载万古霉素涂层的释药性及生物毒性  

Drug-release characteristic and biological toxicity of TiO nanotube/hydroxyapatite loaded vancomycin coating

作　　者：张利兴 田昂[2] 李锡[1] 白希壮[1] Zhang Lixing;Tian Ang;Li Xi;Bai Xizhuang(Department of Sports Medicine and Joint Surgery,People’s Hospital of China Medical University,Shenyang 110016,Liaoning Province,China;School of Materials and Metallurgy,Northeastern University,Shenyang 110819,Liaoning Province,China)

机构地区：[1]中国医科大学人民医院运动医学与关节外科,辽宁省沈阳市110016 [2]东北大学材料与冶金学院,辽宁省沈阳市110819

出　　处：《中国组织工程研究》2021年第10期1500-1506,共7页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(81671811),项目负责人:白希壮。

摘　　要：背景:在钛金属表面改性和涂层化修饰的方案中,表面纳米管改性及羟基磷灰石涂层修饰构建的药物缓释体系具有广阔的临床应用前景。目的:构建载盐酸万古霉素的二氧化钛纳米管/羟基磷灰石复合载药涂层,研究复合涂层的体外药物缓释性能及细胞毒性。方法:以两步阳极氧化法在钛表面制备二氧化钛纳米管涂层,再通过电泳沉积方法制备羟基磷灰石涂层,从而得到钛基表面纳米管/羟基磷灰石的复合涂层结构。随后以该复合涂层为药物承载平台,通过物理吸附方式进行盐酸万古霉素的装载,最终得到载药复合涂层。检测载药二氧化钛纳米管涂层、载药羟基磷灰石涂层、载药复合涂层的体外释药性能。利用不同浓度的载药复合涂层浸提液培养人成骨细胞,采用MTT法检测细胞毒性。将人成骨细胞分别接种于羟基磷灰石涂层、二氧化钛纳米管涂层、载药复合涂层表面,观察细胞形态变化。结果与结论:①相较于载药二氧化钛纳米管涂层与载药羟基磷灰石涂层,载药复合涂层具有更长的药物缓释效能,药物释放时间超过了150 h;②在10%,50%,100%浓度的载药复合涂层浸提液中,成骨细胞的相对活性均>70%,无明显细胞毒性;③3种涂层表面的成骨细胞生长良好,细胞骨架完整,细胞的核质比例正常,与单纯培养的细胞形态无明显无别;④结果表明,二氧化钛纳米管/羟基磷灰石/盐酸万古霉素涂层具有良好的体外药物缓释性能,无明显的细胞毒性。BACKGROUND: In the scheme of titanium surface modification and coating modification, the drug sustained-release system constructed by surface nanotube modification and hydroxyapatite coating modification has broad clinical application prospects. OBJECTIVE: To construct composite drug loading coating of titanium dioxide nanotube/hydroxyapatite loaded with vancomycin hydrochloride, and analyze the drug release performance and cytotoxicity of the composite coating in vitro.METHODS: A two-step anodic oxidation method was used to construct titanium dioxide nanotubes on the titanium surface, and the prepared hydroxyapatite was loaded on the surface of the nanotubes by electrophoretic deposition, so as to obtain a nanotube/hydroxyapatite composite coating structure. Subsequently, the composite coating was used as a drug-loaded platform, and vancomycin hydrochloride was loaded by physical adsorption to finally obtain a composite drug-loaded coating. The in vitro drug release properties of hydroxyapatite/vancomycin hydrochloride, titanium dioxide nanotubes/vancomycin hydrochloride, titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride coating were measured. Human osteoblasts were cultured with titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride coating extracts of different concentrations. MTT assay was used to detect cytotoxicity. Human osteoblasts were inoculated on the surface of hydroxyapatite, titanium dioxide nanotubes, titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride, and the changes of cell morphology were observed. RESULTS AND CONCLUSION:(1) Compared with hydroxyapatite/vancomycin hydrochloride, titanium dioxide nanotube/vancomycin hydrochloride coating, titanium dioxide nanotube/hydroxyapatite/vancomycin hydrochloride coating had a longer drug sustained-release effect. The release time exceeded 150 hours.(2) The 10%, 50%, and 100% concentration of titanium dioxide nanotubes/hydroxyapatite/vancomycin hydrochloride coating extract had no obvious cytotoxicity. The relat

关 键 词：材料 载药涂层 植入材料 感染 电泳沉积 二氧化钛纳米管 羟基磷灰石 药物缓释 细胞毒性 

分 类 号：R459.9[医药卫生—治疗学] R-331[医药卫生—临床医学]