载万古霉素纳米羟基磷灰石对耐甲氧西林金黄色葡萄球菌慢性骨髓炎兔骨缺损的修复

Hydroxyapatite-vancomycin bone cement repairs the defects of chronic osteomyelitis rabbits induced by methicillin-resistant staphylococcus aureus

背景:普通羟基磷灰石植入体内不能完全吸收重建,生物学效应较差,纳米羟基磷灰石更加接近人体骨组织成分,有更好的生物学性能,是良好的可吸收抗生素载体。目的:评价载万古霉素纳米羟基磷灰石治疗耐甲氧西林金黄色葡萄球菌慢性骨髓炎骨缺损的效果。设计、时间及地点:配对分组实验,于2005-10/2006-10在复旦大学中山医院动物实验室完成。材料:同一规格万古霉素纳米羟基磷灰石和单纯纳米羟基磷灰石为自制。30只新西兰大白兔采用髓腔注射耐甲氧西林金黄色葡萄球菌的方法诱导骨髓炎。方法:将30只慢性骨髓炎模型兔配对分为2组,行病灶清创,万古霉素组放入载万古霉素纳米羟基磷灰石,空白材料组放入单纯纳米羟基磷灰石。主要观察指标:分别于1,2,3,6,12周对其进行大体观察,放射影像,细菌培养,病理解剖评价。结果:30只兔均进入结果分析。6周后两组影像学差异明显,万古霉素组的髓内外反应消退,原有的骨干畸形重新正常塑形,空白材料组则出现新的骨内脓肿,骨干畸形加剧。万古霉素组细菌培养阴性,空白材料组阳性。病理切片观察万古霉素组炎症抑制良好,6周后开始恢复正常骨髓结构,纳米羟基磷灰石转化形成小梁结构。结论:纳米羟基磷灰石是万古霉素的良好载体,在良好控制感染的同时,逐步转换成正常骨结构修复病灶骨缺损。

BACKGROUND： Common hydroxyapatite is unsatisfactory for the implant due to incomplete absorption and poor biological effects, while nano-hydroxyapatite cement （HAC） is more close to the human bone tissues and present with good biological performances, thus being considered as excellent absorbable antibiotics cartier. OBJECTIVE： To evaluate the effect of HAC carrying vancomycin in the treatment of chronic osteomyelitis due to methicillin-resistant staphylococcus aureus. DESIGN, TIME AND SETTING： A paired group trial was carried out in the Animal Laboratory, Zhongshan Hospital, Fudan University （Shanghai, China） from October 2005 to October 2006. MATERIALS： Vancomycin-contained HAC and pure HAC were both self-made （China）. Experimental osteomyelitis was induced in the tibia of thirty New Zealand white rabbits by injecting methicillin-resistant staphylococcus aureus. METHODS： All rabbit models of chronic osteomyelitis were categorized into two groups, and were debrided after three weeks. The treatment group were filled with vancomycin-contained HAC, while control group were filled with HAC alone. MAIN OUTCOME MEASURES： Evaluations by gross examination, histology, bacterial culture and radiography in 1, 2, 3, 6 and 12 weeks postoperatively. RESULTS： Thirty rabbits were involved in the final analysis. The different radiographic outcomes between the treatment group and the control group were significant at 6 weeks. The intraosseous and interosseous actions decreased, architectural deformation reformed naturally, and the culture was negative in the treatment group. While the new intraosseous abscess, more deformation and positive culture were found in the control group. Histological observation showed the infection was controlled well, and the natural marrow structure had come back at 6 weeks in the treatment group. The HAC transformed into cancellous bone. CONCLUSION： Nano-HAC is a good carrier material for vancomycin, it can well control the infection and transform into natural bone structures thus healing the bone defects.