Protein-Polyelectrolyte Coacervation

每年，植入医疗设备上的细菌生物膜折磨着成千上万的美国人，并导致数十亿美元的医疗费用增加。这些感染极难杀死，这促使人们对界面涂层进行大量研究，以防止细菌粘附或用化学方法阻碍细菌。然而，这些方法尚未转化为具有较低感染率的设备。这项研究计划的长期目标是消除感染作为植入医疗设备的主要责任。智力优势：中心假设是这些生物膜感染可以通过加热它们生长的设备涂层来热消毒。通过将磁性纳米颗粒固定在涂层中，可以将精确定位的热量无线地直接传递到涂层上，对生长在涂层上的生物膜进行消毒。这一特殊提议的目的是估计在加热过程中邻近组织的温度分布，并证明在这些条件下生物膜的失活。所提出的研究的理由是，了解如何在各种散热器条件下对涂层进行灭菌的同时最大限度地减少热组织损伤，这将转化为一种廉价、通用的医疗植入涂层，可以根据命令进行非侵入性灭菌。为了实现这一目标，本项目将：1)根据给定的热协议估计周围组织的温度分布。涂层将在几个温度下保持几个持续时间，同时记录瞬态温度曲线。将模拟三种极端情况：固定组织、血流和邻近固定组织/大对流血流。这些情景的瞬态温度分布将为计算模型提供信息。2)使用远程激活的磁性纳米颗粒演示等效加热。每个温度/时间协议首先在目标1的三个场景中实现，使用有线电阻，将使用无线磁性纳米粒子负载涂层来实现。薄膜厚度，磁颗粒含量和场强将被改变以符合协议。3)确定每个温度/时间方案的生物膜失活程度。铜绿假单胞菌生物膜将被培养，在每种热沉方案中接受每种温度/时间方案，并对其失活程度进行表征。该项目代表了通过加热消除生物膜的第一次系统尝试，以及首次将磁性超疗应用于基于设备的应用，其中不存在靶向颗粒递送的瓶颈。它为一种新的非侵入性、局部的生物膜感染控制方法提供了基础。更广泛的影响：本项目为处理医疗植入物感染的新方法奠定了基础。有一天，医生可能只需要把一个金属线圈放在病人靠近装置的皮肤上几分钟，就可以让病人回家，而不是需要第二次手术取出植入的装置，然后住院几周，再进行第三次手术植入一个替代品。实现这一愿景的第一步是了解消毒感染所需的温度和暴露时间将如何影响周围组织。对于易受磁影响的器件，可以采用替代加热方法，但无论采用哪种加热方法，对原位功率的要求和对相邻组织的潜在损伤都是相同的。本项目通过实验估计了多种生理情景下的这些项目，并开发了一个模型来预测其他情景下的这些项目。该方法可以推广到大多数种植体类型，而无需对种植体进行重大重新设计，也促进了其与临床的相关性，扩大了其潜在影响的范围。该研究的影响超出了医疗保健行业和相关研究学科。工程和生命科学的紧密结合，再加上工作对较小子项目的适应性，使所提议的工作成为研究生和本科生研究人员特别有价值的教育工具。这种可访问性将用于美国大学的McNair/SROP计划，通过该计划，少数民族，第一代和低收入本科生参加为期8周的全日制研究项目，最终在校际研究会议上结束，在大多数情况下，最终成功申请研究生院。拟议的研究将与McNair/SROP合并，以增加研究界代表性不足的人口的管道。

1133289HoaglandBacterial biofilms on implanted medical devices afflict hundreds of thousands of Americans each year and cause billions of dollars in increased medical costs. These infections are extremely difficult to kill, prompting substantial research efforts on interfacial coatings which would either prevent bacterial adhesion or chemically hinder the bacteria. Theseapproaches have yet to translate to devices with lower infection rates, however. The long term goal of this research program is the elimination of infection as a major liability of implanted medical devices. Intellectual Merit: The central hypothesis is that these biofilm infections can be thermally sterilized by heating the device coating upon which they are growing. By immobilizing magnetic nanoparticles in the coating, precisely localized heat can be wirelessly delivered directly to the coating, sterilizing the biofilm growing on it. The objective for this particular proposal is to estimate the temperature profile of adjacent tissue during this heating and demonstrate biofilm deactivation under these conditions. The ationale for the proposed research is that an understanding of how to minimize thermal tissue damage while sterilizing the coating under a variety of heat sink conditions will translate into an inexpensive, versatile medical implant coating which can be non-invasively sterilized on command. To achieve this objective, this project will: 1) Estimate the temperature profile of surrounding tissue from given thermal protocals. Coatings will be held at a several temperatures for several durations while transient temperature profiles are recorded. Three extreme scenarios will be modeled: immobile tissue, blood flow, and adjacent immobile tissue/large convective blood flow. Transient temperature profiles from these scenarios will inform a computational model. 2) Demonstrate equivalent heating using remotely-activated magnetic nanoparticles. Each temperature/time protocol first achieved in each of the three scenarios in Objective 1 with wired electrical resistors will be achieved using wireless magnetic-nanoparticle-laden coatings. Film thickness, magnetic particle content, and field strength will be altered to match the protocols. 3) Determine degreeof biofilm deactivation from each temperature/time protocol. Pseudomonas aeruginosa biofilms will be ultured, subjected to each temperature/time protocols in each heat sink scenario, and characterized for degree of deactivation. This project represents the first systematic attempt to eliminate biofilms via heat and the first adaptation of magnetic hypertherapy for device-based applications, where the bottleneck of targeted particle delivery does not exist. It provides the basis for a new non-invasive, localized approach to biofilm infection control.Broader Impact: This project lays the foundation for a new way of dealing with medical implant infections. One day, rather than require a second surgery to remove the implanted device, followed by weeks of hospitalization and a third surgery to implant a replacement, the doctor may simply hold a metal coil up to the patients skin near the device for several minutes and send the patient home. One of the first steps toward making this vision a reality is understanding how the temperature and exposure time needed to sterilize the infection will affect the surrounding tissue. Alternative heating approaches can be pursued for magnetically susceptible devices, but regardless of the heating approach, the in situ power requirements and the potential adjacent tissue damage will be the same. This project experimentally estimates those items for multiple physiological scenarios and develops a model for predicting them in other scenarios. The approach can be generalized to most implant types without major redesign of the implant, also facilitating its path to bedside relevance and broadening the scope of its potential impact. The impact of the research goes beyond the health-care industry and related research disciplines. The strong integration of engineering and the life-sciences, coupled with the work's amenability to smaller subprojects, makes the proposed work a particularly valuable educational tool for both graduate and undergraduate researchers. This accessibility will be capitalized for UIs McNair/SROP program, through which minority, first generation, and low-income undergraduates participate in 8-week, full-time research projects culminating in an intercollegiate research conference and, in most cases, eventual successful application to graduate school. The proposed research will be incorporated with McNair/SROP to increase the pipeline of underrepresented populations in the research community.