Protein-Polyelectrolyte Coacervation

蛋白质-聚电解质凝聚

• 批准号: 1133289
• 负责人: David Hoagland
• 金额: $ 30万
• 依托单位: University of Massachusetts Amherst
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2011
• 资助国家: 美国
• 起止时间: 2011-08-15 至 2016-07-31
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1133289&HistoricalAwards=false
• 关键词: Protein; Polyelectrolyte; Coacervation

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.

植入的医疗设备上的细菌生物膜每年折磨着数十万美国人，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，这种涂层要么可以防止细菌黏附，要么可以在化学上阻止细菌。然而，这些方法还没有转化为感染率较低的设备。这项研究计划的长期目标是消除作为植入型医疗器械主要危险因素的感染。智力价值：中心假设是，这些生物膜感染可以通过加热它们生长所在的设备涂层进行热消毒。通过将磁性纳米颗粒固定在涂层中，精确定位的热量可以无线直接传递到涂层，对生长在涂层上的生物膜进行杀菌。这一特定建议的目的是估计在这种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失活。这项拟议的研究的目的是，了解如何在各种散热条件下对涂层进行灭菌的同时将热组织损害降至最低，这将转化为一种廉价、多功能的医用植入物涂层，可以根据需要进行非侵入性灭菌。为了实现这一目标，该项目将：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，同时记录瞬时温度分布。将模拟三种极端情况：静止组织、血液流动和邻近静止组织/大对流血液流动。这些场景的瞬时温度分布将为计算模型提供信息。2)演示使用远程激活的磁性纳米颗粒的等效加热。在目标1中的三种情况中的每一种情况下，首先使用有线电阻实现的每个温度/时间协议都将使用无线磁性纳米颗粒涂层来实现。薄膜厚度、磁粉含量和磁场强度将被改变，以符合协议。3)确定每个温度/时间方案的生物膜灭活程度。铜绿假单胞菌生物膜将被培养，在每个热沉场景中受到不同的温度/时间协议，并表征失活程度。该项目是通过加热消除生物膜的第一次系统尝试，也是第一次将磁超疗法应用于基于设备的应用，在这些应用中，不存在靶向颗粒输送的瓶颈。它为一种新的非侵入性、局部化的方法控制生物被膜感染提供了基础。广泛影响：该项目为处理医疗植入物感染的新方法奠定了基础。有一天，医生不需要进行第二次手术来移除植入的设备，随后需要住院数周，然后再进行第三次手术来植入替代物，医生只需在设备附近将一个金属线圈固定在患者皮肤上几分钟，然后将患者送回家。让这一愿景成为现实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。对于磁敏设备，可以寻求替代的加热方法，但无论采用哪种加热方法，原位功率要求和潜在的邻近组织损伤将是相同的。该项目对多个生理情景下的这些项目进行了实验性的估计，并开发了一个在其他情景中预测这些项目的模型。该方法可以推广到大多数植入物类型，而不需要对植入物进行重大重新设计，也有助于使其与床边相关，并扩大其潜在影响的范围。这项研究的影响超越了医疗保健行业和相关研究学科。工程学和生命科学的紧密结合，加上这项工作对较小的子项目的适应性，使拟议的工作成为对研究生和本科生研究人员特别有价值的教育工具。UIS McNair/SROP计划将利用这种可访问性，通过该计划，少数族裔、第一代和低收入本科生参与为期8周的全日制研究项目，最终将举行校际研究会议，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人群的渠道。