Non-Invasive Local Diagnosis of Surgical Infections

 描述(由申请人提供)：手术部位感染(SSI)已成为一个主要的公共卫生问题。异物(植入物)的存在显著增加了感染的易感性，因为病理微生物与当地宿主细胞竞争附着在外科植入物的表面。这在骨科手术中尤其相关，因为在骨科手术中 仅在美国，每年就有超过250万台设备被植入。诊断和治疗SSI的战略对于抗击这一日益困难的公共卫生问题至关重要。在这个项目中，我们将实施一种非侵入性诊断急性术后感染的新技术。该诊断系统基于我们简单、廉价、无线、可植入的传感器平台。这种小型传感器与植入物集成在一起，只需对植入物本身进行极小的改变或不需要改变。为了检测感染，我们将在我们的简单传感器系统中加入一种对抗菌素敏感的水凝胶，该水凝胶对金黄色葡萄球菌(骨科感染中最常见的微生物)产生的抗原敏感。这种有助于SSI早期诊断的非侵入性经济诊断工具有可能“扰乱”当前SSI的治疗范例，降低成本，改善结果，并减少再入院。由于其简单、小尺寸和最低成本，所提议的系统具有很强的可转换性。最终，传感器有可能降低与手术部位感染相关的发病率和死亡率。在这个项目中，我们将制造抗原敏感的水凝胶，并优化其对金黄色葡萄球菌相关抗原的敏感性，以实现我们的目标特性。我们将在含有纯化抗原的溶液中测试水凝胶，然后在培养中进行测试。使用候选水凝胶，我们将制造包含多种水凝胶配方的无线传感器，并在溶液和培养中对它们进行测试。然后，将在植入物感染模型中进行体内测试。将确定传感器的灵敏度和特异度。

 DESCRIPTION (provided by applicant): Surgical site infections (SSI) have become a major public health concern. The presence of a foreign body (implant) significantly increases susceptibility to infection as pathologic microorganisms compete with local host cells to adhere to the surface of surgical implants. This is particularly relevant in orthopedic surgery where more than 2.5 million devices are implanted annually in the United States alone. Strategies to diagnose and treat SSI are critically important in combating this increasingly difficult public health issue. In this project we will implement a novel technology for non-invasively diagnosing acute post-operative infections. The diagnostic system is based on our simple, inexpensive, wireless, implantable sensor platform. The small sensors are integrated with implants requiring minimal or no alteration to the implant itself. To detect infections, we will incorporate an antige-sensitive hydrogel in our simple sensor system which is sensitive to antigens produced by Staphylococcus aureus (the most common microorganism in orthopedic infections). This non-invasive economical diagnostic tool which facilitates early diagnosis of SSI has the potential to "disrupt" current SSI treatment paradigms, reduce costs, improve outcomes, and reduce readmissions. Because of its simplicity, small size, and minimal cost, the proposed system is highly translational. Ultimately, the sensors have the potential to reduce the morbidity and mortality associated with surgical site infection. In this project, we will fabricate antigen-sensitive hydrogels and optimize their sensitivity to antigens associated with S. aureus to achieve our target properties. We will test the hydrogels in solutions containing purified antigens, then in culture. Using candidate hydrogels, we will fabricate wireless sensors which incorporate multiple formulations of the hydrogel and test them in solution and in culture. S. aureus-sensitive sensors will then be tested in vivo in an implant infection model. Sensor sensitivity and specificity will be determined.