纳米微球负载抗生素/羟基磷灰石复合支架的缓释性能及治疗感染性骨缺损的研究  

Sustained-release properties of nanosphere-loaded antibiotic/hydroxyapatite composite scaffold and its treatment of infectious bone defects

作　　者：王琦 肖善文[1] 杜佳蕾 孙全波[1] 梁健 李相才 Wang Qi;Xiao Shanwen;Du Jialei;Sun Quanbo;Liang Jian;Li Xiangcai(Department of Orthopedics,Affiliated Hospital of Heze Medical College,Heze Shandong,274000,China)

机构地区：[1]菏泽医学专科学校附属医院骨科,山东菏泽274000

出　　处：《生物骨科材料与临床研究》2023年第1期1-7,共7页Orthopaedic Biomechanics Materials and Clinical Study

基　　金：山东省医药卫生科技发展计划项目(2019WS349);菏泽医学专科学校附属医院科研发展计划项目(HYFY202108)。

摘　　要：目的评价新型纳米微球负载抗生素/羟基磷灰石复合支架材料的体外缓释性能及治疗感染性骨缺损的疗效。方法运用HPLC法检测不同时间点药物的体外释放量。建立兔胫骨感染性骨缺损动物模型24只,共分为4组:a组动物仅单纯清创;b组植入1 mg Lev/PMMA;c组植入n-HA/PU;d组植入1 mg Lev/n-HA/PU。在植入材料术后6周、12周观察放射学、组织病理学,Micro CT评价新骨生成。评价新型复合材料控制感染、诱导成骨能力、治疗感染性骨缺损的效果。结果1 mg Lev/n-HA/PU组比1 mg Lev/PMMA组释放的抗生素更多(P<0.05),缓释性能表现更好。单纯清创组X线表现出局部骨破坏、死骨形成。1 mg Lev/n-HA/PU组无明显骨破坏。Micro CT发现1 mg Lev/n-HA/PU组材料周围新生骨小梁数量与其余三组比较,差异有统计学意义(P<0.05),结论新型载抗生素复合支架材料具有良好的缓释性能、抗感染能力、骨诱导能力,可有效治疗胫骨感染性骨缺损。Objective To evaluate the in vitro sustained release properties of novel mesoporous silica microspheres(MSNs) loaded antibiotic/polyurethane(PU)/nano-hydroxyapatite(n-HA)scaffolds and their efficacy in the treatment of rabbit tibia infected bone defects.Methods The scaffolds loaded with 1 mg of levofloxacin mesoporous nanospheres/hydroxyapatite/polyurethane(1 mg Lev/n-HA/PU)and the polymethyl methacrylate(1 mg Lev/PMMA)loaded with 1 mg of levofloxacin were placed on the scaffolds,respectively.In 1 m L of simulated body fluid,the drug release amount was detected at different time points of 1 d,2 d,3 d,4 d,5 d,6 d,1 week(w),2 w,3 w.Twenty-four animal models of chronic osteomyelitis of the tibia were established,and they were divided into 4 groups.Animals in group a were simply debridement;group b was implanted with 1 mg Lev/PMMA;group c was implanted with n-HA/PU;group d was implanted with 1 mg Lev/n-HA/PU.X-ray,Micro CT and histology were observed at 6 W and 12 W postoperatively.To evaluate the efficacy of the new composite material in controlling infection,inducing osteogenesis,and treating chronic osteomyelitis.Results The 1 mg Lev/n-HA/PU group released more antibiotics than the 1 mg Lev/PMMA group(P<0.05),and the sustained release performance was better.X-ray showed that the simple debridement group showed local bone destruction and sequestrum formation.There was no obvious bone destruction in the 1 mg Lev/n-HA/PU group.There was no obvious local inflammatory reaction in the 1 mg Lev/n-HA/PU group.Micro CT found that the number of new bone trabeculae around the material in the 1 mg Lev/n-HA/PU group was significantly different from the other three groups(P<0.05).Conclusion The new antibiotic-loaded composite scaffold has good sustained-release performance,anti-infectious ability,osteoinductive ability,can effectively treat tibial infectious bone defect.

关 键 词：感染性骨缺损 羟基磷灰石 药物缓释 纳米微球 骨组织工程 

分 类 号：R318.08[医药卫生—生物医学工程]