缓释万古霉素三维支架修复兔感染性骨软骨缺损  

Repair of infected osteochondral defect with sustained release vancomycin three-dimensional scaffold in rabbits

作　　者：李兴屿 周杰 李沙沙 张天喜 郭国宁 喻安永 邓江[2] 叶鹏 Li Xingyu;Zhou Jie;Li Shasha;Zhang Tianxi;Guo Guoning;Yu Anyong;Deng Jiang;Ye Peng(Emergency Department of Affiliated Hospital of Zunyi Medical University(First Aid Trauma Ward),Zunyi 563003,Guizhou Province,China;Department of Orthopedics,Zunyi First People’s Hospital,Zunyi 563003,Guizhou Province,China)

机构地区：[1]遵义医科大学附属医院急诊科(急救创伤病区),贵州省遵义市563003 [2]遵义市第一人民医院骨科,贵州省遵义市563003

出　　处：《中国组织工程研究》2024年第22期3509-3516,共8页Chinese Journal of Tissue Engineering Research

基　　金：国家自然科学基金(H0606)地区科学基金,项目名称:SF/CS/nHA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,项目负责人:邓江;贵州省科技计划项目(黔科合支撑[2021]074号),项目名称:基于HIF-1a信号通路NGF-BMSC/ColⅡ/ColⅠ-SF-CS-nHA种植体软骨缺损修复作用机制研究,项目负责人:叶鹏;贵州省科技计划项目(黔科合成果-LC[2022]034),项目名称:Minics虚拟复位联合3D打印技术在胫骨平台shakcz III-VI型骨折中的临床应用研究,项目负责人:郭国宁;遵医附院优秀青年人才培养计划项目(RC220220911),项目负责人:叶鹏。

摘　　要：背景:大量研究证实组织工程支架几乎可完全修复骨软骨缺损,但当骨软骨缺损合并感染时,即使前期经过彻底的清创,单纯骨软骨组织工程支架的修复效果往往不理想。目的:制备盐酸万古霉素缓释微球丝素蛋白/壳聚糖/纳米羟基磷灰石支架,观察其对兔股骨远端感染性骨软骨缺损的修复效果。方法:①采用乳化溶剂挥发法制备盐酸万古霉素缓释微球;将不同质量(7.5,10,12.5 mg)的缓释微球分别与丝素蛋白-壳聚糖-纳米羟基磷灰石溶液混合,利用化学交联法制备盐酸万古霉素缓释微球丝素蛋白/壳聚糖/纳米羟基磷灰石支架,表征支架的孔隙率、吸水膨胀率、热水溶失率及体外药物缓释等。②将45只新西兰大白兔随机分为空白组、对照组、实验组,每组15只,均建立右后肢股骨远端骨软骨缺损并感染模型,空白组不作任何处理,对照组缺损处植入丝素蛋白-壳聚糖-纳米羟基磷灰石支架,实验组缺损处植入盐酸万古霉素缓释微球(10 mg)丝素蛋白/壳聚糖/纳米羟基磷灰石支架。术后1周,检测血液样本C-反应蛋白、白细胞水平;术后4,8,12周取术区组织,分别进行大体观察与病理学观察。结果与结论:①随着缓释微球含量的增加,支架的孔隙率降低,组间比较差异有显著性意义(P<0.05);3组支架的孔径大小、吸水膨胀率、热水溶失率比较差异均无显著性意义(P>0.05);3组支架体外均可持续释放盐酸万古霉素达30 d以上。②实验组兔血液样本C-反应蛋白、白细胞水平均低于空白组、对照组(P<0.05);实验组兔术后各时间点的大体软骨修复情况明显好于空白组、对照组;苏木精-伊红、Masson、阿利新蓝及Ⅱ型胶原免疫组化染色显示,实验组兔术后各时间点的骨软骨修复效果明显优于空白组、对照组。③结果表明,盐酸万古霉素缓释微球丝素蛋白/壳聚糖/纳米羟基磷灰石支架能有效促进开放性骨软骨�BACKGROUND:A large number of studies have confirmed that tissue engineering scaffolds can almost completely repair osteochondral defects.However,when osteochondral defects are complicated with infection,even after thorough debridement in the early stage,the repair effect of simple osteochondral tissue engineering scaffolds is often unsatisfactory.OBJECTIVE:To prepare fibroin/chitosan/nano-hydroxyapatite scaffold loaded with vancomycin hydrochloride sustained release microspheres,and to investigate the repair effect on infected osteochondral defect in distal femur of rabbit.METHODS:(1)Vancomycin hydrochloride sustained release microspheres were prepared by emulsified solvent evaporation method.The sustained-release microspheres of different weights(7.5,10,and 12.5 mg)were mixed with fibroin protein-chitosan nanohydroxyapatite solution,and the scaffolds of fibroin protein/chitosan/nano-hydroxyapatite were prepared by chemical crosslinking method.The porosity,water absorption and expansion rate,hot water loss rate of the scaffolds,and drug sustained-release in vitro were characterized.(2)Forty-five New Zealand white rabbits were randomly divided into blank group,control group,and experimental group,with 15 rabbits in each group.The osteochondral defect and infection model of the distal femur of the right hind limb was established in both groups.The blank group was not treated,and the control group was implanted with fibroin protein-chitosan-nano-hydroxyapatite scaffold.Vancomycin hydrochloride sustained-release microspheres(10 mg)of fibroin/chitosan/nano-hydroxyapatite scaffold were implanted in the defect of the experimental group.The levels of C-reactive protein and leukocytes in blood samples were detected 1 week after operation.At 4,8 and 12 weeks after operation,the tissue of the operative area was taken for gross observation and pathological observation.RESULTS AND CONCLUSION:(1)With the increase of sustained-release microspheres content,the porosity of scaffolds decreased,and there was significant difference

关 键 词：载药微球 万古霉素 骨软骨缺损 组织工程 丝素蛋白 壳聚糖 纳米羟基磷灰石 支架 

分 类 号：R459.9[医药卫生—治疗学] R318.08[医药卫生—临床医学] R-331