Lawson McKinley C, Bowman Christopher N, Anseth Kristi S
Department of Chemical and Biological Engineering, University of Colorado, Boulder, CO 80309, USA.
Clin Orthop Relat Res. 2007 Aug;461:96-105. doi: 10.1097/BLO.0b013e3180986706.
Infections in the setting of orthopaedic hardware remain a serious complication. Traditional treatment modalities rely on antibiotic-loaded biomaterials and/or prolonged intravenous therapy, both of which suffer major limitations. We hypothesized a derivatized form of the glycopeptide antibiotic vancomycin could be covalently attached to a Ti-6Al-4V implant alloy to form a bactericidal surface capable of killing bacteria relevant to orthopaedic infections. First, a polymerizable poly(ethylene glycol)-acrylate derivative of vancomycin was synthesized. This monomer was characterized by liquid chromatography, 1H NMR spectroscopy, and MIC and MBC determination. The monomer was subsequently photochemically polymerized to implant grade Ti-6Al-4V alloy. The coating was bactericidal against Staphylococcus epidermidis through initial release of unattached antibiotic species followed by continued surface-contact-mediated bacterial killing by covalently tethered vancomycin. Through this surface-contact mechanism, the number of colony forming units dropped by ca. fivefold from an initial inoculum of 1 x 10(6) cfu/mL over 4 hours and by ca. 100-fold with respect to nonbactericidal control surfaces. An inoculum of 1 x 10(4) cfu/mL was reduced to undetectable levels over 17 hours. This coating method allows a loading dose several thousand times larger than that achieved with monolayer vancomycin coupling approaches and holds promise for the treatment of orthopaedic infections.
骨科植入物相关感染仍然是一种严重的并发症。传统的治疗方式依赖于负载抗生素的生物材料和/或延长静脉治疗时间，而这两种方法都存在重大局限性。我们推测，糖肽类抗生素万古霉素的一种衍生形式可以共价连接到Ti-6Al-4V植入合金上，形成一个能够杀死与骨科感染相关细菌的杀菌表面。首先，合成了一种可聚合的万古霉素聚（乙二醇）-丙烯酸酯衍生物。该单体通过液相色谱、1H核磁共振光谱以及最小抑菌浓度（MIC）和最小杀菌浓度（MBC）测定进行表征。随后，该单体通过光化学聚合到植入级Ti-6Al-4V合金上。该涂层通过未附着抗生素的初始释放以及随后通过共价连接的万古霉素持续进行表面接触介导的细菌杀灭，对表皮葡萄球菌具有杀菌作用。通过这种表面接触机制，在4小时内，菌落形成单位数量从初始接种量1×10(6) cfu/mL下降了约五倍，相对于非杀菌对照表面下降了约100倍。1×10(4) cfu/mL的接种量在17小时内降至检测不到的水平。这种涂层方法允许的负载剂量比单层万古霉素偶联方法高出数千倍，有望用于治疗骨科感染。
