载药微球联合BMP-2治疗兔慢性骨髓炎的实验研究

Experimental study on the drug loaded microspheres combined with BMP-2 in the treatment of chronic osteomyelitis in rabbits

目的探讨载药纳米羟基磷灰石/壳聚糖(n-HA/CS)新型植入材料治疗慢性骨髓炎的可行性。方法将60只健康新西兰大白兔分为4组构建骨髓炎模型,按以下方法植入材料,A组:不做任何处理;B组:单纯n-HA/CS支架材料;C组:nHA/CS载万古霉素脂质体种植体;D组:n-HA/CS载万古霉素脂质体种植体与BMP-2。8周后通过细菌培养及组织病理学检测,评价其抗感染能力及修复骨缺损的能力。结果载药n-HA/CS人工植入材料能够释放高浓度的抗菌药物;植入载药n-HA/CS联合BMP-2可有效控制骨感染并促进骨组织的修复;治疗效果明显优于单纯载药n-HA/CS材料组及单纯n-HA/CS材料组。结论载药n-HA/CS联合BMP-2是治疗兔慢性骨髓炎的较为理想的植入材料。

Objective To investigate the anti‐infection and bone repair effects of cationic liposome‐encapsulatedvancomycin combined with the nano‐hydroxyapatite/chitosan（n‐HA/CS） composite scaffold in vivo .Methods Sixty 6‐month‐old New Zealand white rabbits ,weighing 2 .5 kg ,were selected to prepare chronic infectious tibia bone defect model by using Staphylococcus aureus . After 4 weeks ,60 survival rabbits were randomly divided into 4 groups（n=15） .After debridement ,defect was treated with nothing in group A ,with n‐HA/CS composite scaffold in group B ,with vancomycin and n‐HA/CS composite scaffold in group C ,and with cationic liposome‐encapsulated vancomycin and n‐HA/CS composite scaffold in group D .After 8 weeks of treatment ,general obser‐vation ,X‐ray ,HE staining .Results At 4 weeks after modeling ,60 rabbits were diagnosed as having osteomyelitis ,including perios‐teal new bone formation ,destruction of bone ,and soft tissue swelling .At 8 weeks after treatment ,sinus healed in group C and D ,but sinus was observed in group A and B ;the gross bone pathologieal scores of group D were significantly better than those of group A and B（P〈0 .05） .Bone defects were repaired completely in group D ,the results of the longest diameter of bone defects in group D was significantly better than those in the other 3 groups （P〈0 .05） .New bone formation was observed in group C and D ,but peri‐osteal reaction and marrow low‐density shadow were observed in group A and B;Norden score in group D was significantly better than those in group A ,B ,and C（P〈0 .05） .HE staining showed that there were a large number of trabecular bone formation and fi‐brosis ,with no obvious signs of infection in group C and D ,but neutrophil accumulation was observed in group A and B ;Smeltzer in group C and D were significantly better than those in group A and B（P〈0 .05） .Bacteriological results showed higher negative rate in group C and D than in groups A and B（P〈0 .05） .Conclusion Cationic liposome‐encapsulated vancomyc and n‐HA/CS compos‐ite scaffold can be a good treatment for infectious bone defects in rabbits ,providing a new strate 3 for the therapy of bone defects in chronic infection .