NSF/FDA SIR: Using Microbial Signaling Systems to Understand Relationship Between Microbial Growth an d Breast Implant Complications

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Breast augmentation is one of the most popular surgical cosmetic procedures nationwide, with over $1.1 billion spent on silicone gel implants in 2018. However, breast implants are not lifetime devices and the longer patients have breast implants, the higher the risk of complications. Recent studies show that biofilms, microbial communities that grow on surfaces, are associated with these complications. At the center of the discussion is BIA-ALCL (breast implant-associated anaplastic large cell lymphoma/cancer) which recently triggered a series of regulatory actions worldwide. Recent studies suggest that the higher surface area of textured implants provide more opportunity for bacteria to colonize into biofilms, which could stimulate a cascade of immune responses including chronic inflammation, one of the possible pathogenesis of BIA-ALCl. The goal of this one-year Scholar-in-Residence project is to study the impact of a special set of molecules known to regulate bacteria activity, termed “quorum sensing molecules," on BIA-ALCL. The project’s findings are expected to provide information that aids in the review of new strategies to control and inhibit bacterial infection in breast implants. These findings will also be integrated into existing K-12 outreach activities occurring at Howard Middle School. This proposed research will support a female graduate student from Howard University engaged in highly interdisciplinary research and a new collaboration between Howard University and the Food and Drug Administration.This project is focused on the impact of quorum sensing (QS) molecules on BIA-ALCL. Microbial communities use QS molecules to coordinate microbial community function. QS molecules are often used to regulate biofilm formation and can be associated with a T-Cell response in certain types of organisms, though current knowledge on immune response to QS molecules is nascent. The research plan is designed to advance knowledge on the link between microbial community quorum sensing capacity and malignancies. The central hypothesis of this work is that QS can regulate biofilm formation in textured implants. The investigators will employ bioinformatic, experimental, and computational models to assess this hypothesis with three objectives: (1) Conduct a review and bioinformatic analysis on breast implant microbiota, (2) Develop a drip flow biofilm reactor system to evaluate how biofilms response to molecular cues, and (3) Develop a computational model system to evaluate how biofilms respond to material cues. The expected outcome is an understanding of differences in the microbial structure and function as it relates to quorum sensing capacity in implants of different patients. The bioinformatics analysis could serve as a case study on how to utilize high-throughput tools to facilitate regulatory review of permanent implants. The model system will provide information that aids in the review of new strategies to control and inhibit bacterial infection in breast implants.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.