Carbon Nantotubes as Antimicrobial Agents

CBET-0756323P。可植入的医疗器械/材料正变得司空见惯，通常在救生过程中扮演着重要角色。医疗器械感染仍然是一个重大的悬而未决的问题。表现出抗菌行为的材料是一种有吸引力的解决方案，但由于抗感染药物的数量有限、释放速度逐渐减小、释放的化合物的毒性等原因，目前涉及抗感染药物持续输送的策略是次优的。更好的方法是由一种永久的、不可溶出的抗菌物质组成的材料。PI和Co-PI在这里建议研究碳纳米管(CNT)作为潜在的抗菌材料的构建块。最近，两名研究人员(LP和ME)表明，CNT可以有效地杀灭细菌，但仍与人类细胞兼容。这些新的发现，再加上碳纳米物体典型的化学稳定性和易于功能化，使碳纳米管作为抗菌材料的构建块具有潜在的吸引力。然而，目前对碳纳米管抗菌作用的基础知识非常有限。例如，以下关键的基本问题仍然悬而未决：-碳纳米管的性质--长度、直径、表面功能化、金属含量--如何影响它们的抗菌活性？-碳纳米管的呈现--作为孤立的纳米管、沉积的聚集体、薄膜--如何影响它们的抗菌活性？--碳纳米管通过什么机制发挥抗菌活性(S)？研究人员试图在这里回答这些问题，从而朝着设计基于碳纳米管的抗菌材料迈出第一步。重点是已知的四种感染生物医学设备的模型病原体，该团队在能够生产直径精确控制的低缺陷碳纳米管的独特位置开始了该项目。能够在不使用抗生素或其他潜在有害(生物)化学制剂的情况下摧毁有害病原体的材料可能会给医疗保健带来革命性的变化--对人类生活质量产生巨大影响。人们还可以想象，使用这里开发的策略，其他表面--卫生保健设施甚至家庭内--也将具有抗感染能力。对细胞-纳米管相互作用的机械理解--在这里是在微生物的背景下发展的，但未来可能扩展到人类细胞--也可能有助于医学应用的发展，如生物传感器、药物输送、组织工程支架以及靶向和摧毁癌细胞。调查人员建议将本科生纳入拟议的研究活动。学生将来自耶鲁大学、纽黑文大学和阿尔伯特斯·马格努斯学院(都在纽黑文)。来自耶鲁大学明星项目的学生尤其受欢迎，该项目旨在支持少数族裔和女性理工科学生的本科生研究。该团队还建议通过将耶鲁工程纳入耶鲁医学院和护理学院与希尔地区职业高中之间的现有合作伙伴关系，来开展与纽黑文公立高中的外联工作。鼓励参与的本科生担任高中生的导师。将研究纳入耶鲁大学本科生和研究生课程也将产生广泛影响。研究人员提议开发一个关于纳米管合成和表面涂层的课程模块，包括一系列讲座，作为现有的纳米和生物材料本科生和研究生课程的一部分。其重要意义将是及早接触纳米技术中最先进的方法，以及刺激跨学科的课堂互动。

CBET-0756323P. Van Tassel, Yale UniversityImplantable medical devices/materials are becoming commonplace, often playing major roles in life-saving procedures. Medical device infection continues to be a significant unresolved problem. Materials exhibiting antimicrobial behavior represent an attractive solution, but current strategies involving the sustained delivery of anti-infective agents are sub-optimal due to finite quantity of anti-infective, gradually diminishing rate of release, toxicity of released compound, etc. A superior approach would be a material composed of a permanent, non-leachable antimicrobial substance. The PI and co-PIs propose here to investigate carbon nanotubes (CNT) as potential building blocks for antimicrobial materials. Recently, two of the investigators (LP and ME) have shown CNT to effectively kill bacteria, yet to remain compatible with human cells. These new findings, together with the chemical stability and ease of functionalization typical of carbon nanoscale objects, make CNT potentially attractive as building blocks for antimicrobial materials. However, fundamental knowledge of the CNT antimicrobial effect is currently very limited. For example, the following key fundamental questions remain open: - How do CNT properties - length, diameter, surface functionalization, metal content - influence their antimicrobial activity? - How does CNT presentation - as isolated nanotubes, deposited aggregates, thin films - influence their antimicrobial activity? - By what mechanism(s) do CNT exert antimicrobial activity? The investigators seek here to answer these questions and thereby take the first steps toward engineering CNT-based antimicrobial materials. The focus is on four model pathogens known to infect biomedical devices, and the team begins the project in a unique position of being able to produce low-defect CNT of precisely controlled diameter. Materials capable of destroying harmful pathogens without the use of antibiotics or other potentially harmful (bio)chemical agents could revolutionize health care - yielding an immense impact on the quality of human life. One could also imagine other surfaces - within health care facilities or even households - being rendered anti-infective using the strategies developed here. A mechanistic understanding of the cell-nanotube interaction - here developed in the context of microbes but possibly extended in the future to human cells - could also aid in the development of medical applications such as biosensors, drug delivery, tissue engineering scaffolds, and targeting and destruction of cancer cells. The investigators propose to integrate undergraduate students into the proposed research activities. Students will come from Yale, the University of New Haven, and Albertus Magnus College (all in New Haven). Students from the STARS program at Yale, a program to support undergraduate research for minority and female science/engineering students, are especially sought. The team also proposes to develop an outreach effort to a New Haven public high school by adding Yale Engineering to an existing partnership between the Yale Schools of Medicine and Nursing and the Hill Regional Career High School. The participating undergraduate students will be encouraged to act as mentors to the high school students. Integration of research into the Yale undergraduate and graduate curricula will also have a broad impact. The investigators propose to develop a course module on nanotube synthesis and surface coating consisting of a series of lectures to be given as part of existing undergraduate and graduate courses on nano- and bio-materials. The significance will be an early exposure to state-of-the art methods in nanotechnology, as well as stimulating interdisciplinary classroom interaction.