Implantable 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.
