表面改性工程化融合器调控椎间界面骨溶解机制的研究  

The preliminary investigation on mechanism of preventing spinal interface osteolysis via surface-modified tissue-engineered cage

作　　者：郭洪刚[1] 冯世庆[1] 周悦彬 姚芳莲[2] 刘印忠[3] 陈治 梁玉柱 汪涛[1] Guo Honggang;Feng Shiqing;Zhou Yuebin;Yao Fanglian;Liu Yinzhong;Chen Zhi;Liang Yuzhu;Wang Tao(Department of Orthopedic Surgery,General Hospital of Tianjin Medical University,Tianjin 300052,China;College of Chemical Engineering,Tianjin University y Tianjin 300072,China;?College of Pharmacy,Tianjin Medical University,Tianjin 300070,China;College of Precision Instruments and Optoelectronic Engineering,Tianjin University,Tianjin 300072,China)

机构地区：[1]天津医科大学总医院骨科,300052 [2]天津大学化学工程学院,300072 [3]天津医科大学药理学院,300070 [4]天津大学精密仪器与光电子工程学院,300072

出　　处：《中华实验外科杂志》2019年第12期2250-2253,共4页Chinese Journal of Experimental Surgery

基　　金：国家自然科学基金(81272013)。

摘　　要：目的评估椎间界面炎性与破骨基因表达趋势.方法按表面改性与常规模式构建工程化融合器(cage),建立羊颈前路融合模型,移植6组,每组14只:表面改性的工程化cage、常规组织工程化cage、非表面改性β-磷酸三钙/壳聚糖/聚己内酯(β-TCP/CS/PCL)cage、羟基磷灰石(HA)cage、钛合金及异体骨cage.第2、4、8、12、16、20、24、28、36周行3D CT检查,分析骨矿化沉积率、新骨面积及成骨细胞数量;分析白细胞介素(IL)-6、基质金属蛋白酶-1(MMP-1)、肿瘤坏死因子-α(TNF-α)、抗酒石酸酸性磷酸酶(TRAP)、核心结合因子α1(Runx2)/成骨特异性转录因子/Cbfα1抗体及成骨蛋白(OPG)基因表达及力学特性.结果表面改性cage组新骨增殖活跃,骨矿化沉积率、新骨面积及成骨细胞数量[(63.9±1.3)%、(76.5±1.8)%、(73.8±2.3)个]均优于其他组[(45.1±2.1)%、(53.6±0.3)%、(61.1±1.6)个,F=7.495、5.967、5.459,P<0.05].IL-6、MMP-1、TNF-α及TRAP基因表达(0.09±0.01、0.13±0.02、0.08±0.01)减弱,Runx2及OPG基因表达(0.73±0.13、0.57±0.16)增强,骨结构强度及活动范围指标[(4.38±0.25)Nm/degree、(6.55±0.19)°]优于其他组,差异有统计学意义(t=7.596、13.220,P<0.05).结论表面改性工程化cage能消除骨溶解,预防界面无菌性松动.Objective To evaluate the interrelationship between intervertebral osteolysis and inflammatory or osteoclastic gene expresion.Methods Adipose derived stromal cells(ADSCs)were osteoinduced,conventioanl tissue-engineered(TE)and surface-modified TE cage constructs were establisehd.Anterior cervical fusion model of goat was established.Implantation was carried out according to following six group:surface-modified TE cage group[Nd:YAG+RGD+p-tricalcium phosphate(B-TCP)/chitosan(CS)/polycaprolactone(PCL)cage+ADSCs],TE cage group(0-TCP/CS/PCL cage+ADSCs),non-modified p-TCP/CS/PCL cage,hydroxyapatite(HA)cage,titanium and bone allograft cage.Three-dimensional CT was used to observe morphology changing,bone mineralization ratio,new bone mension and osteoblatic quantity,interleukin-6(IL-6),metalloprotease-1(MMP-1),tumor necrosis factor-α(TNF-a)and tartrate resistant acid phosphatase(TRAP),and osteoprotein(OPG)gene expression were detected at 2,4,8,12,16,20,24,28 and 36 weeks.Biomechanical property was also detected at different interval.Results Compared with other groups,implant subsidence and migration were not found in surface-modified TE cage group.Meanwhile,new bone prolifreated remarkably with satisfactory data of bone mineralization ratio,and new bone mension or osteoblatic quantit[(63.9±1.3)%,(76.54±1.8)%,(73.8±2.3)ceUs].IL-6,MMP-1,TNF-a and TRAP gene downregulated(0.09±0.01,0.13±0.02,0.08±0.01).Conversely,Runx2 and OPG gene upregulated(0.73±0.13,0.57±0.16).In addition,data of bone strength and rang of motion in surface-modified TE cage group were significantly higher than those of other groups[(4.38±0.25)Nm/degree,(6.55±0.19)°].Conclusion Invertebral osteolysis can be effectively controlled by surface-modified TE approach,and this provides a potential therapy for implant aseptic loosening.

关 键 词：骨溶解 融合器 表面改性 组织工程 界面 

分 类 号：R68[医药卫生—骨科学]