As of February 2017, the FDA had received 359 medical device reports (MDRs) of breast implant associated anaplastic large cell lymphoma (BIA-ALCL), including nine deaths. Among the 231 reports that had information about the implant surface, 203 were reported to be textured implants and 28 were reported to be smooth implants. It has been hypothesized that BIA-ALCL may be caused by bacterial colonization and formation of biofilms (multicellular structures of attached cells) on breast implants. However, it is not clear why textured implants have a specific association with ALCL. It is also not known how to improve the safety of these implants. This challenge is largely due to the knowledge gap in the fundamental understanding of how surface topography affects microbial adhesion and biofilm formation, as well as the lack of guiding principles for the design of antifouling topographies. The teams at Syracuse University and FDA will collaborate to address this challenge and gain critical new knowledge through complementary studies. Specifically, the team will collaborate to investigate how bacteria respond to surface topography during attachment and how to engineer new surfaces to prevent bacterial attachment. The results of this project will provide new knowledge and valuable information to FDA about what types of surfaces are more likely to be colonized, which will be useful for FDA's regulation of novel anti-biofilm topographies. In addition to research, the team will also leverage this project to promote student training, especially the individuals from underrepresented groups; and educate the next generation of engineers to be leaders solving challenging technical and societal problems to improve human health and well being.
Bacteria attach to implanted medical devices using flagella, pili, and other factors such as adhesins. The attachment of microbes leads to the subsequent formation of a biofilm, which is a surface-attached multicellular structure comprised of an extracellular matrix secreted by the attached cells. Biofilm infections are difficult to treat because of extremely high tolerance of biofilm cells to antimicrobials and disinfectants (up to 1000 times higher compared to their planktonic counterparts). Since properties of the substratum material such as surface chemistry, stiffness, hydrophobicity, roughness, topography, and charge affect bacterial adhesion, biofilm formation may be inhibited by tailoring these properties. However, previous research on biofilm control by altering surface topography is largely empirical and lacks a mechanistic understanding of how bacteria make a decision between planktonic growth and biofilm formation by sensing and responding to surface topography. In addition, the engineered antifouling topographies to date are largely static and cannot move. Even if a small number of bacteria cells attach, they can multiply and gradually overcome most anti-biofilm topographies. To more effectively control biofouling, it is important to engineer new dynamic materials that can change surface topography upon an environmental cue. A dynamic material can both prevent initial bacterial adhesion and disrupt established biofilms, causing the colonizers to disperse into planktonic form where they can be eradicated by the host immune system and antibiotic treatment. The team hypothesizes that specific micron-scale surface topographies can be rationally designed to inhibit bacterial biofilm formation while promoting the adhesion of mammalian cells. It is also hypothesized that established biofilms can be removed by dynamic changes in such surface topographies via on-demand triggering when needed. The team will test these hypotheses by studying how bacteria respond to different surface topographies using Escherichia coli, Pseudomonas aeruginosa, and Staphylococcus aureus as model species.
This award reflects NSF's statutory mission and has been deemed worthy of support through evaluation using the Foundation's intellectual merit and broader impacts review criteria.