可注射型磷酸镁骨水泥生物相容性及体外模型中性能表现的评价

Biocompatibility and mechanical properties of an injectable magnesium phosphate cement in ex vivo model

目的通过体内外实验评价可注射型磷酸镁骨水泥(MPC)的生物相容性及其强化体外羊经皮椎体后凸成形术(PKP)模型的能力,探讨MPC作为PKP骨替代物的潜能。方法采用酸碱反应原理合成MPC。分别在MPC和聚甲基丙烯酸甲酯(PMMA)骨水泥材料表面接种SD大鼠成骨细胞,经电镜扫描了解不同材料的细胞相容性。使用万能试验机测定MPC固化试样的抗压强度,采用称重法测定MPC膏体的可注射性。将36个羊L4～6椎骨均分为3组:A组椎骨不予处理(阳性对照组),B组和C组椎体行PKP造模,C组椎骨注入MPC填充缺损,B组作为空白对照组,于MPC注入后2、24、48、72h测定3组椎体的轴向最大载荷。使用新西兰兔行双侧股骨髁缺损造模,分别以PMMA骨水泥和MPC填充双侧缺损,术后1、3、6、12周取材,经微CT扫描观察2种材料的生物体内相容性。结果 MPC在细胞接种后4、24h时表面均有细胞黏附,24h时表面黏附细胞伸展,形态学良好;PMMA材料表面黏附细胞数目少,黏附细胞的形态学较差。MPC抗压强度为(30.16±1.22)MPa,可注射性为99.69%±0.32%。体外PKP模型实验结果显示,MPC注入2、24、48、72h时C组椎体轴向最大载荷均显著高于B组椎体[分别为(4.360±0.036)kN对(3.480±0.085)kN、(4.640±0.106)kN对(3.480±0.040)kN、(4.740±0.026)kN对(3.477±0.093)kN、(4.740±0.040)kN对(3.480±0.026)kN,P均<0.05]。新西兰兔体内试验微CT扫描结果显示,MPC与PMMA未引发明显的排异反应、炎症和感染征象,在第12周MPC出现一定程度降解,而PMMA无降解征象。结论 MPC表现出良好的力学强度和可注射性,细胞相容性和动物体内相容性良好,体外PKP模型中MPC的机械性能表现良好,具有成为PKP骨替代物的潜能。

Objective To assess biocompatibility of an injectable magnesium phosphate cement(MPC)via in vivo and in vitro experiments and test its capability to enhance the strength of an ex vivo goat percutaneous kyphoplasty(PKP)model,to reveal its potential to be a PKP bone substitute.Methods MPC was synthesized by acid-base reaction.Osteo-progenitor cells of SD rats were seeded on MPC and polymethyl methacrylate(PMMA)in order to observe the cytocompatibility of those materials using scanning electron scope.Compressive strength of solidified samples was measured with an universal test instrument,and injectability of MPC cream was evaluated by weighing method.The L4-L6 lumbar vertebras obtained from 36 goats were divided into 3 groups randomly,with group A untreated as a positive control.PKP models were created in both group B and group C,with the vertebra bodies in group B filled with nothing as a blank control and those in group C filled with MPC.The maximal axial load of vertebra were tested in all three groups at 2 h,24 h,48 hand 72 hafter MPC was injected.Bone defects were in the femoral condyles in New Zealand white rabbits and then were filled with PMMA or MPC.Micro CT scanning was performed to observe the biocompatibility of both materials at 1 st,3 rd,6 th and 12 th week postoperatively.Results Four hours and 24 hafter cells were seeded,cells adhered on MPC surface on both time points,and at 24 hthese cells stretched well,exhibiting good morphology.There were only a few cells adhered on PMMA surface,and the morphology of adhered cells was not good.Compressive strength of the MPC was(30.16±1.22)MPa,and injectability of it was 99.69%±0.32%.In ex vivo experiments,the maximal axial load of vertebra in group C was significantly higher than that in group B at 2 h[(4.360±0.036)kN vs(3.480±0.085)kN],24 h[(4.640±0.106)kN vs(3.480±0.040)kN],48 h[4.740±0.026 kN vs(3.477±0.093)kN],72 h[(4.740±0.040)kN vs(3.480±0.026)kN]after MPC injection,respctively(all P<0.05).Micro CT scanning results showed that obvious rejection reaction,inflammation and infection were not observed in either MPCfilling or PMMA-filling groups in the New Zealand white rabbits;MPC exhibited degradation to some extent while PMMA showed no sign of degradation.Conclusion MPC exhibited good mechanical strength,injectability,cytocompatibility,in vivo compatibility and performed well in ex vivo model.It is promising to be an alternative bone substitute in PKP.