Price J S, Tencer A F, Arm D M, Bohach G A
Harborview Medical Center, Department of Orthopedics, Seattle, Washington, USA.
J Biomed Mater Res. 1996 Mar;30(3):281-6. doi: 10.1002/(SICI)1097-4636(199603)30:3<281::AID-JBM2>3.0.CO;2-M.
Chronic osteomyelitis is one of the most serious complications of orthopedic open fracture treatment. The objective of this study was to develop a biodegradable implant coating with impregnated antibiotics as an adjunct to current therapy. We used a polylactic-co-glycolic acid copolymer (PLGA) as the biodegradable carrier and gentamicin as the antibiotic. Our objectives were to establish elution characteristics of the antibiotic from the polymer, and determine if the coated orthopedic implants would inhibit bacterial growth in vitro. In the elution study, coated implants were incubated in phosphate buffered saline (PBS) at 37 degrees C and sampled daily for gentamicin levels. The in vitro model consisted of test tubes containing Mueller-Hinton culture broth inoculated with 5 x 10(6) cfu of Staphylococcus aureus and incubated at 37 degrees C. The implants were switched to a new set of inoculated tubes each day. Tubes were sampled for colony counting to determine bactericidal effects. Implant coatings consisted of 40 mg of gentamicin as a 20% mixture with PLGA. The elution curve showed an average level of 138 micrograms/mL over 15 days. This local concentration would be more than adequate to kill susceptible organisms. The in vitro study showed a significant reduction in bacterial growth in the test tubes containing coated implants. Control tubes averaged 2.5 x 10(8) cfu/mL of S.aureus over 24 days. Coated implant tubes averaged 0.9 cfu/mL. This was a reduction of greater than 99.999% (p < 0.0001). This study showed that a thin biodegradable implant coating can be developed with bactericidal activity against the organisms frequently associated with osteomyelitis in cases of open fractures.
慢性骨髓炎是骨科开放性骨折治疗中最严重的并发症之一。本研究的目的是开发一种浸渍抗生素的可生物降解植入物涂层，作为当前治疗的辅助手段。我们使用聚乳酸-乙醇酸共聚物（PLGA）作为可生物降解载体，庆大霉素作为抗生素。我们的目标是确定抗生素从聚合物中的洗脱特性，并确定涂层骨科植入物在体外是否能抑制细菌生长。在洗脱研究中，将涂层植入物在37℃的磷酸盐缓冲盐水（PBS）中孵育，每天取样检测庆大霉素水平。体外模型由装有接种了5×10⁶ cfu金黄色葡萄球菌的Mueller-Hinton培养液的试管组成，并在37℃下孵育。每天将植入物更换到一组新的接种试管中。对试管进行取样以进行菌落计数，以确定杀菌效果。植入物涂层由40mg庆大霉素与PLGA按20%的比例混合组成。洗脱曲线显示在15天内平均水平为138μg/mL。这种局部浓度足以杀死易感微生物。体外研究表明，含有涂层植入物的试管中细菌生长显著减少。对照试管在24天内金黄色葡萄球菌的平均浓度为2.5×10⁸ cfu/mL。涂层植入物试管平均为0.9 cfu/mL。这一减少幅度大于99.999%（p<0.0001）。本研究表明，可以开发出一种薄的可生物降解植入物涂层，对开放性骨折病例中常见的与骨髓炎相关的微生物具有杀菌活性。
