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万古霉素阳离子脂质体联合纳米羟基磷灰石/壳聚糖/魔芋葡甘聚糖支架治疗兔感染性骨缺损

[Vancomycin cationic liposome combined with nano-hydroxyapatite/chitosan/konjac glucomannan scaffold for treatment of infected bone defects in rabbits].

作者信息

Huang Jinliang, Ma Tao, Tang Hui, Fan Xinyu, Xu Yongqing

机构信息

Orthopedic Center, Kunming General Hospital of Chengdu Military Command, Kunming Yunnan, 650032, PR China.

出版信息

Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2012 Feb;26(2):190-5.

Abstract

OBJECTIVE

To investigate the anti-infection and bone repair effects of cationic liposome-encapsulated vancomycin combined with the nano-hydroxyapatite/chitosan/konjac glucomannan (n-HA/CS/KGM) composite scaffold in vivo.

METHODS

Fifty-one 6-month-old New Zealand white rabbits, weighing 1.5-3.0 kg, were selected to prepare chronic infectious tibia bone defect model by using Staphylococcus aureus. After 4 weeks, 48 survival rabbits were randomly divided into 4 groups (n=12). After debridement, defect was treated with nothing in group A, with n-HA/CS/KGM composite scaffold in group B, with vancomycin and n-HA/CS/KGM composite scaffold in group C, and with cationic liposome-encapsulated vancomycin and n-HA/CS/KGM composite scaffold in group D. After 8 weeks of treatment, general observation, X-ray, HE staining, the bacterial culture, and the measurement of the longest diameter of bone defect were done.

RESULTS

At 4 weeks after modeling, 48 rabbits were diagnosed as having osteomyelitis, including periosteal new bone formation, destruction of bone, and soft tissue swelling. The Norden score was 3.83 +/- 0.52. At 8 weeks after treatment, sinus healed in groups C and D, but sinus was observed in groups A and B; the gross bone pathological scores of group D were significantly better than those of groups 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 groups C and D, but periosteal reaction and marrow low-density shadow were observed in groups A and B; Norden score in group D was significantly better than those in groups A, B, and C (P < 0.05). HE staining showed that there were a large number of trabecular bone formation and fibrosis, with no obvious signs of infection in groups C and D, but neutrophil accumulation was observed in groups A and B; Smeltzer scores in groups C and D were significantly better than those in groups A and B (P < 0.05). Bacteriological results showed higher negative rate in groups C and D than in groups A and B (P < 0.05).

CONCLUSION

Cationic liposome-encapsulated vancomycin and n-HA/CS/KGM composite scaffold can be a good treatment for infectious bone defects in rabbits, providing a new strategy for the therapy of bone defects in chronic infection.

摘要

目的

探讨阳离子脂质体包裹的万古霉素联合纳米羟基磷灰石/壳聚糖/魔芋葡甘聚糖(n-HA/CS/KGM)复合支架在体内的抗感染及骨修复作用。

方法

选取51只6月龄、体重1.5 - 3.0 kg的新西兰白兔,采用金黄色葡萄球菌制备慢性感染性胫骨骨缺损模型。4周后,48只存活兔随机分为4组(n = 12)。清创后,A组不做处理,B组用n-HA/CS/KGM复合支架处理,C组用万古霉素和n-HA/CS/KGM复合支架处理,D组用阳离子脂质体包裹的万古霉素和n-HA/CS/KGM复合支架处理。治疗8周后,进行一般观察、X线检查、HE染色、细菌培养以及测量骨缺损最长径。

结果

建模后4周,48只兔均诊断为骨髓炎,表现为骨膜新生骨形成、骨质破坏及软组织肿胀。Norden评分为3.83±0.52。治疗8周后,C组和D组窦道愈合,而A组和B组可见窦道;D组的大体骨病理评分显著优于A组和B组(P < 0.05)。D组骨缺损完全修复,D组骨缺损最长径的结果显著优于其他3组(P < 0.05)。C组和D组可见新骨形成,而A组和B组可见骨膜反应及骨髓低密度影;D组的Norden评分显著优于A组、B组和C组(P < 0.05)。HE染色显示,C组和D组有大量小梁骨形成及纤维化,无明显感染迹象,而A组和B组可见中性粒细胞聚集;C组和D组的Smeltzer评分显著优于A组和B组(P < 0.05)。细菌学结果显示,C组和D组的阴性率高于A组和B组(P < 0.05)。

结论

阳离子脂质体包裹的万古霉素和n-HA/CS/KGM复合支架可有效治疗兔感染性骨缺损,为慢性感染性骨缺损的治疗提供了新策略。

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