Gerhart T N, Roux R D, Horowitz G, Miller R L, Hanff P, Hayes W C
Department of Orthopaedic Surgery, Charles A. Dana Research Institute, Boston, Massachusetts.
J Orthop Res. 1988;6(4):585-92. doi: 10.1002/jor.1100060417.
An experimental biodegradable bone cement [poly(propylene fumarate)-methylmethacrylate] (PPF-MMA) has been compared in vivo with polymethylmethacrylate (PMMA) as a carrier agent for local release of antibiotics. This approach is potentially applicable to the treatment of chronic osteomyelitis where the clinical goal is to achieve sustained high concentrations of antibiotics locally in the infected bone. In our experiments, gentamicin- and vancomycin-impregnated cylindrical PMMA and PPF-MMA cement specimens were implanted subcutaneously in rats, and blood and wound fluid samples were obtained over a 2-week period. Antibiotic levels were determined using immunoassays, and microbiologic activity was confirmed with agar diffusion techniques. The biodegradable PPF-MMA cement achieved and maintained considerably higher wound antibiotic levels than did PMMA cement. Vancomycin levels for the PPF-MMA cement were greater than 20 times those for the PMMA cement at all sampling times from 24 h to 14 days. For both cements, the serum antibiotic concentrations remained safely below maximum levels recommended for parenteral therapy. Mechanical testing of the PPF-MMA cement showed that admixture of 3% by weight of antibiotic did not adversely affect material properties. We conclude that this experimental biodegradable bone cement (PPF-MMA) can be used as a carrier to achieve high sustained local levels and low serum levels of antibiotics. Because it is biodegradable and thus does not require a secondary procedure for removal, it has special potential for use in treatment of chronic osteomyelitis.
一种实验性可生物降解骨水泥聚富马酸丙二醇酯-甲基丙烯酸甲酯已在体内与聚甲基丙烯酸甲酯(PMMA)进行比较,作为抗生素局部释放的载体。这种方法可能适用于慢性骨髓炎的治疗,其临床目标是在感染骨中局部实现抗生素的持续高浓度。在我们的实验中,将含庆大霉素和万古霉素的圆柱形PMMA和PPF-MMA骨水泥标本皮下植入大鼠体内,并在2周内采集血液和伤口液样本。使用免疫测定法测定抗生素水平,并用琼脂扩散技术确认微生物活性。可生物降解的PPF-MMA骨水泥在伤口处达到并维持了比PMMA骨水泥高得多的抗生素水平。在从24小时到14天的所有采样时间,PPF-MMA骨水泥的万古霉素水平比PMMA骨水泥高20倍以上。对于两种骨水泥,血清抗生素浓度均安全地低于肠胃外治疗推荐的最高水平。PPF-MMA骨水泥的力学测试表明,按重量计3%的抗生素混合物不会对材料性能产生不利影响。我们得出结论,这种实验性可生物降解骨水泥(PPF-MMA)可作为载体,实现抗生素在局部的高持续水平和低血清水平。由于它是可生物降解的,因此不需要二次手术取出,在慢性骨髓炎治疗中具有特殊的应用潜力。