Ehrlich Garth D, Stoodley Paul, Kathju Sandeep, Zhao Yongjun, McLeod Bruce R, Balaban Naomi, Hu Fen Ze, Sotereanos Nicholas G, Costerton J William, Stewart Philip S, Post J Christopher, Lin Qiao
Center for Genomic Sciences, Allegheny Singer Research Institute, Pittsburgh, PA 15212, USA,
Clin Orthop Relat Res. 2005 Aug(437):59-66. doi: 10.1097/00003086-200508000-00011.
Artificial joints are subject to chronic infections associated with bacterial biofilms, which only can be eradicated by the traumatic removal of the implant followed by sustained intravenous antibiotic therapy. We have adopted an engineering approach to develop electrical-current-based approaches to bacterial eradication and microelectromechanical systems that could be embedded within the implanted joint to detect the presence of bacteria and to provide in situ treatment of the infection before a biofilm can form. In the former case we will examine the combined bactericidal effects of direct and indirect electrical fields in combination with antibiotic therapy. In the latter case, bacterial detection will occur by developing a microelectromechanical-systems-based biosensor that can "eavesdrop" on bacterial quorum-sensing-based communication systems. Treatment will be effected by the release of a cocktail of pharmaceutical reagents contained within integral reservoirs associated with the implant, including a molecular jamming signal that competitively binds to the bacteria's quorum sensing receptors (which will "blind" the bacteria, preventing the production of toxins) and multiple high dose antibiotics to eradicate the planktonic bacteria. This approach is designed to take advantage of the relatively high susceptibility to antibiotics that planktonic bacteria display compared with biofilm envirovars. Here we report the development of a generic microelectromechanical systems biosensor that measures changes in internal viscosity in a base fluid triggered by a change in the external environment.
人工关节易受到与细菌生物膜相关的慢性感染,只有通过创伤性取出植入物并随后进行持续静脉抗生素治疗才能根除。我们采用了一种工程方法来开发基于电流的细菌根除方法和微机电系统,这些系统可以嵌入植入关节内,以检测细菌的存在,并在生物膜形成之前对感染进行原位治疗。在前一种情况下,我们将研究直接和间接电场与抗生素治疗相结合的杀菌效果。在后一种情况下,将通过开发一种基于微机电系统的生物传感器来进行细菌检测,该传感器可以“窃听”基于细菌群体感应的通信系统。治疗将通过释放与植入物相关的整体储库中所含的药物试剂混合物来实现,其中包括一种分子干扰信号,该信号与细菌的群体感应受体竞争性结合(这将“蒙蔽”细菌,阻止毒素的产生)以及多种高剂量抗生素来根除浮游细菌。这种方法旨在利用浮游细菌与生物膜环境变体相比对抗生素具有相对较高敏感性的特点。在此,我们报告了一种通用微机电系统生物传感器的开发,该传感器可测量由外部环境变化触发的基础流体内部粘度的变化。