负载抗生素的纳米三维支架修复大段骨缺损  

A three-dimensional nano-scaffold carrying antibiotics for large-segmental bone defects

作　　者：叶鹏[1,2] 黄文良[3] 邓江[3] 邓崇第[1] 张天喜[1] 喻安永[1] 余斌[2] Ye Peng;Huang Wen-liang;Deng Jiang;Deng Chong-di;Zhang Tian-xi;Yu An-yong;Yu Bin(Emergency Trauma Ward,Affiliated Hospital of Zunyi Medical College,Zunyi 563003,Guizhou Province,China;Department of Orthopedic Trauma,Nanfang Hospital of Southern Medical University,Guangzhou 510515,Guangdong Province,China;Department of Orthopedic Trauma,Third Affiliated Hospital of Zunyi Medical College,Zunyi 563003,Guizhou Province,China)

机构地区：[1]遵义医学院附属医院急救创伤病区,贵州省遵义市563003 [2]南方医科大学附属南方医院创伤骨科,广东省广州市510515 [3]遵义医学院第三附属医院创伤骨科,贵州省遵义市563003

出　　处：《中国组织工程研究》2018年第30期4812-4817,共6页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(H0606)地区科学基金项目:SF/CS/n HA仿生支架结合骨软骨镶嵌移植术和PRP对大面积骨软骨缺损修复的研究;国家自然科学基金(A226)地区科学基金项目:脾源性炎症反应介导的小胶质细胞活化在创伤性脑水肿形成中的作用及机制;贵州省省长基金项目[2011(25)]:rhBMP-2缓释系统/自体松质骨复合生物支架修复骨缺损的研究~~

摘　　要：背景:前期研究证明利用壳聚糖、丝素蛋白、纳米羟基磷灰石可以制备出具有一定机械性能的纳米三维支架材料。目的:在前期研究基础上,将左氧氟沙星负载于丝素蛋白/壳聚糖/纳米羟基磷灰石三维支架上,观察其对开放性长骨骨干骨缺损的抗感染及修复效果。方法:将36只新西兰大白兔随机分3组,每组12只。3组均于右侧桡骨中段建立长2.0 cm骨缺损,实验组植入负载抗生素的纳米三维支架材料,对照组植入纳米三维支架材料,空白组未植入任何材料,植入后4个月,进行骨缺损区X射线及组织学检查。结果与结论:(1)植入后1个月,实验组伤口无局部感染化脓,对照组、空白组均出现了局部软组织炎症反应甚至死亡;(2)植入后4个月,实验组骨组织影像学表现与正常骨组织无明显区别,支架完全由正常骨组织替代,有骨髓腔再通;对照组可见骨痂生长,骨质密度低于实验组,未见骨髓腔再通;空白组支架断端已封闭,停止生长,骨折不愈合;(3)苏木精-伊红染色显示,实验组可见成骨细胞成群排列在基质中,细胞形态良好;对照组可见骨细胞、骨基质,还可见新生毛细血管,处于骨髓腔再通早期;空白组可见纤维结缔组织及肌纤维组织生长;实验组Lane-Sandhu组织学评分高于对照组、空白组(P<0.05);(4)结果表明,负载抗生素的丝素蛋白/壳聚糖/纳米羟基磷灰石三维支架在兔桡骨大段骨缺损修复中显示出了良好的抗感染能力、骨支架及骨诱导作用。BACKGROUND:Previous studies have shown that a three-dimensional nano-scaffold with mechanical performance can be prepared using silk fibroin(SF),chitosan(CS),and nanohydroxyapatite(n-HA).OBJECTIVE:To explore the anti-infection and repair ability of the SF/CS/n-HA three-dimensional scaffold loaded with levofloxacin for the treatment of open long bone defects.METHODS:Thirty-six New Zealand white rabbits were randomized into three groups(n=12 per group).An animal model of 2.0 cm bone defect in the right middle humerus was made in each rabbit,followed by implantation of SF/CS/n-HA three-dimensional scaffold loaded with levofloxacin in experimental group,three-dimensional nano-scaffold in control group and nothing in blank control group.X-ray and histological observations of the bone defect region were performed at 4 months after implantation.RESULTS AND CONCLUSION:(1)No infection or suppuration occurred in the experimental group at 1 month after implantation,but inflammatory reactions and even death happened in the control and blank control groups.(2)In the experimental group,imaging findings of the defected long bone showed no distinct difference from the normal bone tissues at 4 months after implantation.The scaffold in the experimental group was completely replaced by normal bone tissue accompanied by the recanalization of the bone marrow cavity.The control group showed bone callus growth,but the bone density was lower than that in the experimental group,and moreover,there was no recanalization of the medullary cavity.The blank control group exhibited closed ends of the scaffold,terminated growth of bone tissue,and fracture nonunion.(3)Hematoxylin-eosin staining results revealed that:in the experimental group,osteoblasts in the matrix arranged in clusters with good cell morphology;in the control group,there were bone cells,bone matrix,and new capillaries,and the medullary cavity of the fractured bone achieved recanalization;in the blank group,fibrous connective tissues and muscle fiber tissues were seen.The histol

关 键 词：纳米三维支架 左氧氟沙星 骨组织工程 纳米羟基磷灰石 骨感染 生物材料 抗菌药 氧氟沙星 羟基磷灰石类 组织工程 

分 类 号：R318[医药卫生—生物医学工程]