去甲万古霉素活性煅烧骨颗粒的体外缓释与体内修复骨缺损研究

Experimental studies on the slow- release of active ceramics bone particles with norvancomycin and its effect on repairing impaired bone

目的:将异种煅烧骨、Ⅰ型胶原、骨形成蛋白、去甲万古霉素制备为活性缓释材料后与骨水泥复合,探讨其体外缓释万古霉素和体内对兔感染性桡骨缺损的修复作用。方法:采用体外洗提实验和抑菌实验观察缓释系统体外释放能力。建立兔感染桡骨缺损模型,使用缓释材料修复骨缺损,通过X线检查、组织学观察、生物力学测定和扫描电镜等手段观察抗感染和成骨情况。结果:缓释系统体外洗提实验结果,1d时平均浓度为(474.5±46.8)μg/mL,30d时为(8.9±1.5)μg/mL。缓释系统的体外抑菌实验结果,抑菌圈1d平均直径为(22.1±1.6)mm,30d为(5.9±0.3)mm。X线检查和组织学观察显示缓释材料有较强的抗感染修复能力。扫描电镜观察缓释材料有较高的空隙率。生物力学测量结果显示,缓释材料修复兔桡骨最大扭转强度平均为(0.82±0.03)Nm,接近自体骨组的(0.76±0.05)Nm(P>0.05),明显高于煅烧骨组的(0.26±0.01)Nm(P<0.05)。实验组最大弯曲载荷平均为(172.2±6.1)N,接近自体骨组的(162.6±4.1)N(P>0.05),明显高于煅烧骨组的(46.8±6.8)N(P<0.05)。结论:缓释材料具有较强的缓释药物能力和抗感染修复成骨能力,可望成为新型骨缺损修复材料。

Objective A new type of bone graft material was constructed by true bone ceramics composed with type Ⅰ collagen, bone morphogenetic protein and norvancomycin. To explore the effect of slow-dellverlng norvaneomycin in this new type material on repairing impaired rabbit radius induced by infection. Methods The release of this material in vitro was determined by the concentration of norvancomycin in the elution fluids determined by high performance liquid chromatography and the inhibitory zones. In order to observe osteogenesis in the radius and the degradation process of material, a series of examination were carried out including radiography, histomorphological detection, biomechanical detection, and scanning electronic microscopy. Results The concentration of norvancomycin in the elution fluids was （474. 5 ± 46.8） μg/mL on the 1st day and （8.9 ± 1.5）μg/mL on the 30th day. The inhibitory zone was （22.1 ± 1.6）mm on the 1st day and （5.9 ± 0. 3） mm on the 30th day. Radiography and histological detection showed this slow-releasing material had a strong capacity of anti-infection and repair. Scanning electronic microscopy demonstrated there was much interspace with this material. Biomechanical detection showed the mean maximal intensity of torsion of the rabbit radius repaired by this slow-releasing material was （0. 82 ± 0. 03）Nm, closing to （0.76 ± 0. 05）Nm in the autogenous bone group （ P 〉 0.05）, much higher than （0.26 ± 0. 01 ） Nm in the ceramics bone group （ P 〈 0. 05）. The mean maximal load of bending of the rabbit radius repaired by this slow-releasing material was （172.2 ± 6.1 ）N, closing to （162.6 ± 4.1 ）N in the autogenous bone group （ P 〉 0. 05）, much higher than （46.8 ± 6.8） N in the ceramics bone group （ P 〈 0. 05） . Conclusion The new slow-releasing compound has great potential of anti-infection and repairing impaired bone and can be used as new bone graft substitute in the clinical management.