A biodegradable delivery system for antibiotics and recombinant human bone morphogenetic protein‐2: A potential treatment for infected bone defects
A biodegradable delivery system for antibiotics and recombinant human bone morphogenetic protein‐2: A potential treatment for infected bone defects
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DOI：
10.1002/jor.20049
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发表时间：
2006-03
影响因子：
2.8
通讯作者：
A. Suzuki;H. Terai;H. Toyoda;T. Namikawa;Yoshiko Yokota;Takanori Tsunoda;K. Takaoka
中科院分区：
文献类型：
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作者：
A. Suzuki;H. Terai;H. Toyoda;T. Namikawa;Yoshiko Yokota;Takanori Tsunoda;K. Takaoka
为了生产用于治疗感染性骨不连或骨缺损的成骨和杀菌生物材料，将合成的可降解聚D，L-乳酸片段与随机插入的对二氧环己酮和聚乙二醇（PLA-DX-PEG）片段的嵌段共聚物与重组人BMP-2（rhBMP-2）和高浓度抗生素混合。然后，我们检查了抗生素（替考拉宁）从聚合物中的体外洗脱曲线、抗生素对rhBMP-2的骨诱导能力或rhBMP诱导的异位新骨形成的影响，以及聚合物在大鼠颅骨缺损模型中修复骨的能力。约40%的替考拉宁在前24小时内释放，剩余量在21天内稳定释放，抗菌活性未丧失。在孵育期结束时，聚合物在磷酸盐缓冲盐水（pH 7.4）中降解消失。含抗生素和rhBMP-2的颗粒的体内性能显示，3周后听小骨内的骨产量无显著变化。此外，抗生素对rhBMP 2修复颅骨缺损的能力没有抑制作用。事实上，当缺损用载有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，并在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与rhBMP-2一样有效。此外，无论是否存在抗生素，rhBMP-2的生物活性均得以保留。© 2006骨科研究学会。出版社：Wiley Periodicals，Inc. J Orthop Res 24：327-332，2006
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. © 2006 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 24:327–332, 2006