载万古霉素缓释微球纳米羟基磷灰石/壳聚糖支架联合自体红骨髓可修复慢性骨髓炎兔的骨缺损  

Repair of bone defects due to chronic osteomyelitis in rabbits using nano-hydroxyapatite/chitosan scaffold carrying vancomycin/polyactic-co-glycolic acid sustained-release microspheres combined with autologous red bone marrow

作　　者：向柄彦[1] 李鹏[1] 柏帆[1] 周思睿[1] Xiang Bingyan;Li Peng;Bo Fan;Zhou Sirui(the First People’s Hospital of Zunyi, Zunyi 563000, Guizhou Province, China)

机构地区：[1]遵义市第一人民医院,贵州省遵义市563000

出　　处：《中国组织工程研究》2019年第6期843-848,共6页Chinese Journal of Tissue Engineering Research

基　　金：遵义市联合科技基金项目[2017(42)];项目负责人:向柄彦~~

摘　　要：背景:前期研究证实,万古霉素缓释微球对兔慢性骨髓炎具有良好的治疗效果,纳米羟基磷灰石/壳聚糖具有良好的生物相容性、降解性及成骨诱导性,自体红骨髓联合纳米羟基磷灰石/壳聚糖支架可用于修复兔桡骨骨缺损。因此,3者联合修复兔慢性骨髓炎骨缺损的效果有待验证。目的:探讨载万古霉素/聚乳酸-羟基乙酸共聚物(polyactic-co-glycolicacid,PLGA)缓释微球的纳米羟基磷灰石/壳聚糖支架,联合自体红骨髓修复兔慢性骨髓炎骨缺损的治疗效果及可行性。方法:采用水-油-水乳相法制备万古霉素/PLGA缓释微球,将缓释微球与纳米羟基磷灰石/壳聚糖混合液充分混匀,采用真空冷冻干造法制备载万古霉素/PLGA缓释微球的纳米羟基磷灰石/壳聚糖支架,对支架进行力学性能测试及万古霉素释放量检测。在20只5月龄新西兰大白兔(解放军第三军医大学大坪医院实验动物中心提供)左侧胫骨髓腔内注射金黄色葡萄球菌,构建慢性骨髓炎骨缺损模型,随机分4组干预,A组仅作清创处理,B组清创后植入纳米羟基磷灰石/壳聚糖支架,C组清创后植入载万古霉素/PLGA缓释微球纳米羟基磷灰石/壳聚糖支架,D组清创后植入载万古霉素/PLGA缓释微球纳米羟基磷灰石/壳聚糖支架及自体红骨髓。治疗3个月后,通过X射线、病理苏木精-伊红染色评价骨缺损修复效果。结果与结论:(1)载万古霉素/PLGA缓释微球的纳米羟基磷灰石/壳聚糖支架,具有良好的生物力学性能及缓慢平稳释放万古霉素的能力;(2)治疗3个月后的X射线显示,A、B组胫骨近端仍见明显的缺损区、骨质破坏及骨膜反应;C组可见新生骨形成,缺损区稍模糊,但仍有缺损存在;D组可见新骨形成,缺损区模糊,密度稍增高,骨膜反应消失;(3)治疗3个月后的病理苏木精-伊红染色显示,A、B组骨小梁紊乱、破坏较多;C、D组骨小梁排列较为整齐,破坏较少,且D组骨BACKGROUND:Preliminary studies have confirmed that vancomycin sustained-release microspheres exert satisfactory therapeutic effect on chronic osteomyelitis in rabbits.Nano-hydroxyapatite/chitosan(nHA/CS)has good biocompatibility,degradability and osteogenic induction.Autologous red bone marrow can be used as a seed cell source combined with nHA/CS scaffold to repair rabbit tibia bone defects.Therefore,the combined effects of the three materials in the repair of rabbit chronic osteomyelitis bone defects need a further investigation.OBJECTIVE:To explore the efficacy and feasibility of nHA/CS scaffold carrying vancomycin/polyactic-co-glycolic acid(PLGA)sustained-release microspheres combined with autologous red bone marrow in the repair of chronic osteomyelitis bone defects in rabbits.METHODS:Vancomycin/PLGA sustained-release microspheres were prepared by water oil and water emulsion method.The nHA/CS scaffolds carrying vancomycin/PLGA sustained-release microspheres were prepared by vacuum freeze drying,and mechanical properties and vancomycin release of the scaffold were determined.Twenty5-month-old New Zealand white rabbits provided by Laboratory Animal Centre of Daping Hospital of Third Military Medical University were selected for establishing the chronic osteomyelitis bone defect model by intramedullary infection of Staphylococcus aureus into the left tibia.The model rabbits were randomly divided into four groups:group A was only given only for debridement treatment;in group B,the nHA/CS scaffold was implanted after debridement;in group C,nHA/CS scaffolds carrying vancomycin/PLGA sustained-release microspheres were implanted after debridement;in group D,nHA/CS scaffolds carrying vancomycin/PLGA microspheres and autologous red bone marrow were implanted after debridement.At3months after implantation,the repair effect was observed by X-ray and hematoxylin-eosin staining.RESULTS AND CONCLUSION:The nHA/CS scaffolds carrying vancomycin/PLGA sustained-release microspheres held good biomechanical properties and drug s

关 键 词：纳米羟基磷灰石 壳聚糖 万古霉素 缓释微球 慢性骨髓炎 自体红骨髓 骨髓炎骨缺损 复合支架 羟基磷灰石类 微球体 骨髓炎 骨髓 组织工程 

分 类 号：R459.9[医药卫生—治疗学] R318.06[医药卫生—临床医学]