Pre-clinical in vitro and in vivo studies to examine the potential use of photodynamic therapy in the treatment of osteomyelitis
Pre-clinical in vitro and in vivo studies to examine the potential use of photodynamic therapy in the treatment of osteomyelitis
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DOI：
10.1039/b507082a
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发表时间：
2006-01-01
影响因子：
3.1
通讯作者：
Burch, S
中科院分区：
文献类型：
--
作者：
Bisland, SK;Chien, C;Burch, S
由于真菌或细菌感染引起的骨骼和邻近结构的急性或慢性炎症，骨髓炎可导致严重的发病率甚至死亡。在美国，发病率每年约为每1000名新生儿和每5000名儿童中就有一名，在患有糖尿病或镰状细胞性贫血的成年人中，发病率分别上升至0.36%和16%。目前的治疗方案包括抗生素和/或手术。然而，抗生素耐药病原体数量的增加表明，需要替代策略。我们正在研究光动力疗法(PDT)作为骨髓炎的一种替代治疗方法，使用生长在克氏针(K-wire)上的生物发光金黄色葡萄球菌(S.aureus)。采用亚甲蓝(MB)或5-氨基酮丙酸(ALA)介导的光动力疗法(PDT)，在体外或植入SD大鼠胫骨髓腔后，将涂有金黄色涂层的K线暴露于其中。利用生物发光非侵入性地监测金黄色葡萄球菌生物膜的进展，并在治疗前立即表示为每个样本的信号百分比。金黄色葡萄球菌感染在接种后第10天接受光动力疗法。治疗包括：在4h后，通过放置在胫骨上的光纤经皮下注射ALA(300 mg kg(-1))，然后用光(635+/-10 nm；75J cm(-2))照射，导致细菌生长明显延缓。在体外，MB和ALA表现出相似的细胞杀伤，其细胞杀伤为~gt；=4log(10)。在体内，ALA介导的PDT抑制了骨中的生物膜植入。这些结果证实了MB或ALA介导的PDT具有利用骨髓炎动物模型治疗体外或体内培养的金黄色葡萄球菌的潜力。
Osteomyelitis can lead to severe morbidity and even death resulting from an acute or chronic inflammation of the bone and contiguous structures due to fungal or bacterial infection. Incidence approximates 1 in 1000 neonates and 1 in 5000 children in the United States annually and increases up to 0.36% and 16% in adults with diabetes or sickle cell anaemia, respectively. Current regimens of treatment include antibiotics and/or surgery. However, the increasing number of antibiotic resistant pathogens suggests that alternate strategies are required. We are investigating photodynamic therapy (PDT) as one such alternate treatment for osteomyelitis using a bioluminescent strain of biofilm-producing staphylococcus aureus ( S. aureus) grown onto kirschner wires (K-wire). S. aureus-coated K-wires were exposed to methylene blue (MB) or 5-aminolevulinic acid (ALA)-mediated PDT either in vitro or following implant into the tibial medullary cavity of Sprague-Dawley rats. The progression of S. aureus biofilm was monitored non-invasively using bioluminescence and expressed as a percentage of the signal for each sample immediately prior to treatment. S. aureus infections were subject to PDT 10 days post inoculation. Treatment comprised administration of ALA (300 mg kg(-1)) intraperitoneally followed 4 h later by light ( 635 +/- 10 nm; 75 J cm(-2)) delivered transcutaneously via an optical fiber placed onto the tibia and resulted in significantly delay in bacterial growth. In vitro, MB and ALA displayed similar cell kill with >= 4log(10) cell kill. In vivo, ALA-mediated PDT inhibited biofilm implants in bone. These results confirm that MB or ALA-mediated PDT have potential to treat S. aureus cultures grown in vitro or in vivo using an animal model of osteomyelitis.