Suzuki Akinobu, Terai Hidetomi, Toyoda Hiromitsu, Namikawa Takashi, Yokota Yoshiko, Tsunoda Takanori, Takaoka Kunio
Department of Orthopaedic Surgery, Osaka City University Graduate School of Medicine, 4-3 Asahi-machi, Osaka 545-8585, Japan.
J Orthop Res. 2006 Mar;24(3):327-32. doi: 10.1002/jor.20049.
To produce an osteogenic and bacteriocidal biomaterial for the treatment of infected nonunions or bone defects, a synthetic degradable block copolymer of poly-D,L-lactic acid segments with randomly inserted p-dioxanone and polyethylene glycol (PLA-DX-PEG) segments was mixed with recombinant human BMP-2 (rhBMP-2) and antibiotics at high concentration. We then examined the in vitro elution profile of an antibiotic (teicoplanin) from the polymer, the effects of antibiotics on the bone-inducing capacity of rhBMP-2 or on ectopic new bone formation induced by the rhBMP, and the ability of the polymer to repair bone in a rat cranial defect model. Approximately 40% of teicoplanin was released within the first 24 h, with the remaining amount released steadily over 21 days with no loss of antibacterial activity. The polymer had disappeared by degradation in the phosphate buffered saline (pH 7.4) at the end of the incubation period. The in vivo performance of pellets with antibiotics and rhBMP-2 revealed no significant change in bone yield within the ossicles after 3 weeks. Also, antibiotics had no inhibitory effect on the ability of rhBMP2 to repair cranial defects. Indeed, when the defect was filled by a polymer disc loaded with rhBMP-2 with or without teicoplanin, the defect was repaired by new bone, and normal anatomy was restored within 6 weeks. In conclusion, the PLA/DX/PEG polymer appears to work as effectively for antibiotics as it does for rhBMP-2. Additionally, the biological activity of rhBMP-2 was retained irrespective of the presence of antibiotics.
为制备一种用于治疗感染性骨不连或骨缺损的具有成骨和杀菌作用的生物材料，将聚-D,L-乳酸链段与随机插入的对二氧环己酮和聚乙二醇（PLA-DX-PEG）链段的合成可降解嵌段共聚物与重组人骨形态发生蛋白-2（rhBMP-2）及高浓度抗生素混合。然后我们检测了抗生素（替考拉宁）从聚合物中的体外洗脱曲线、抗生素对rhBMP-2骨诱导能力或对rhBMP诱导的异位新骨形成的影响，以及该聚合物在大鼠颅骨缺损模型中修复骨的能力。替考拉宁约40%在最初24小时内释放，其余部分在21天内稳定释放，且抗菌活性无损失。在孵育期结束时，聚合物在磷酸盐缓冲盐水（pH 7.4）中因降解而消失。含抗生素和rhBMP-2的微丸的体内性能显示，3周后小骨内的骨产量无显著变化。此外，抗生素对rhBMP2修复颅骨缺损的能力没有抑制作用。实际上，当缺损用负载有rhBMP-2（含或不含替考拉宁）的聚合物圆盘填充时，缺损由新骨修复，6周内恢复正常解剖结构。总之，PLA/DX/PEG聚合物对抗生素的作用似乎与对rhBMP-2的作用一样有效。此外，无论是否存在抗生素，rhBMP-2的生物活性均得以保留。
