Each year, millions of medical devices with different surface textures are used to provide life support, mitigate failing body parts, or for cosmetic purposes. Recent research has revealed that surface topography has profound impact on microbe-material interactions and thus the safety of implanted medical devices. However, the mechanisms of such interactions and how to rationally design surface topographies to prevent infection while promoting host tissue integration are not well understood. This study is motivated by this knowledge gap and the recent reports of breast implant associated anaplastic large cell lymphoma (BIA-ALCL). BIA-ALCL is a well-recognized complication that has devastating impact on affected individuals, which has led to a decision of the Food and Drug Association (FDA) in 2019 to remove certain breast implants from the market. Despite this well-recognized challenge, the cause of BIA-ALCL remains elusive and a guideline for effectively regulating such devices is still missing. Through a prior Scholar-in-Residence at FDA project, the PI Ren and FDA co-PI Philips have obtained important new information about how bacteria interact with surface topographies, which led to this proposed new project. Through close collaboration, the team will conduct the first study on how implant surface topography affects bacterial quorum sensing and production of virulence factors, as well as the effects of surface topography on phagocytosis. The findings from this study will not only benefit the safety of breast implants, but also help guide the design and regulation of other devices. Beyond the research itself, the team will leverage this project to recruit young talents especially those from underrepresented groups and jointly advise graduate students. This project will help workforce development and better prepare civilly responsible engineers to solve challenging problems facing our society.
During previous study, the team discovered that surface topographies mimicking the features of ALCL-associated breast implants have significantly higher bacterial loads than the flat control and the surfaces with other recessive patterns tested. In addition, the cell density in recessive wells were about 7 times higher than the flat control based on two-dimensional surface coverage after just 24 hours of culturing. The difference can be even bigger considering the three-dimensional biofilm structure and interaction with host factors, which will be studied in this project. Based on these findings, the team hypothesizes that inappropriate recessive features can promote bacterial biofilm formation, quorum sensing, and associated production of virulence factors. The team further hypothesizes that these topographic features present a physical hindrance for immune cells such as macrophages from reaching bacterial cells and cleaning them from the implant surface, leading to inflammation and subsequently BIA-ALCL. The team will test these hypotheses by conducting complementary experiments and cell tracking to understand how surface topography affects the interaction between bacteria and host cells. This new information will fill an important knowledge gap, and provide critical insights for understanding device-associated complications and the design of safer medical devices. The results will help FDA to better prepare for reviews of emerging technologies involving smart biomaterials. The team will also leverage this project to motivate students for research, especially individuals from underrepresented groups.
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.