利福平-异烟肼-控释型载药人工骨的实验研究

Experimental Study of a Rifampicine-isoniazidcontrolled Release Drug Implant

开发研究一种能承载多药并有控释特性的载药人工骨。利用三维打印技术，制备具有多层同心圆柱体结构的载药人工骨，并将利福平和异烟肼由内到外按特定顺序加载，观察微观结构、孔隙率、体外药物释放特性和体外细胞生物相容性。所制备的载药人工骨呈多孔结构，孔隙率（61．76±2．53）％、微孔孔径50—100μm，体外药物呈现序贯释放，双药释放峰值依次交替出现，持续释放时间超过50d，NTT检测示细胞毒性0级，电镜观察细胞生长分化良好，并有大量细胞黏附于载药人工骨表面；三维打印技术可以精确地制备具有复杂结构的载药人工骨，制备的多药控释型载药人工骨具有药物缓释和序贯控释的特性，同时具有良好的孔隙率和细胞相容性，为骨结核治疗提供一种新型有效的手段。

This study is aimed to investigate a controlled release multi-drug implant for bone tuberculosis therapy. 3D printing technology was used to fabricate a drug implant with a multi-layered concentric cylinder construction. Rifampicine and isonicotinic acid hydrazide were placed in a special sequence from the center to the periphery simultaneously. The micro-construction, porosity, drug release property and cytocompatibility were observed in vitro. The controlled release multi-drug implant fabricated by 3D printing were completely coincident with the predefined construction. A multi-aperture construction was detected by ESEM with a porosity of （61.76±2.53）% and micropore diameters ranged from 50-100 μm. An orderly drug release from the outside to the center were detected in the drug release assays in vitro and the release remained over 50 days ; The cytotoxic level detected in MTT assay was 0, and BMSCs cell shave dramatically reproduced and almost covered the whole wall of drug implant. 3D printing technology could fabricate a complex construction drug implant precisely. The drug implant with a multi-layered concentric construction possessed potential capabilities in multi-drugs therapeutic alliance, controlled or programmed drug release, and ideal cytocompatibility, which might offer a new and effective method for bone tuberculosis therapy.