CAREER: Topography-mediated Immunomodulation for Implant-associated Infections

About This Grant

Implant-associated infections are a significant challenge in healthcare, affecting millions of patients and often leading to severe complications such as implant failure, tissue damage, and even amputation. These infections cost healthcare systems billions of dollars annually in revision surgeries and related treatments. Current antimicrobial strategies focus primarily on killing bacteria but often overlook the role of the body’s immune system, which plays a crucial role in infection control. Upon implantation, biomaterials can disrupt the immune system, causing excessive inflammation and increasing infection risks. This CAREER project seeks to address these challenges by exploring how the physical properties of biomaterials, particularly surface topographies or patterns, affect the behavior of immune cells and their interactions with pathogens. Although surface nano- and micro-patterning is commonly used in medical devices such as implants (e.g., orthopedic, dental, breast) and catheters to improve performance, its effects on immune defenses and infection risk are largely unknown. By studying how topography affects host–pathogen interactions in both 2D and 3D settings, this research will provide deeper insights into the relationships between biomaterials, host cells, and bacteria. These findings will establish new design rules for biomaterials that can enhance immune defenses, fight infections, and improve implant success. Furthermore, the research program will be integrated with a collaborative education and outreach plan, including STEAM (Science, Technology, Engineering, Art, and Mathematics) initiatives and public outreach activities, to increase awareness about the importance of biomaterials and implant infections while promoting STEM education and interdisciplinary learning. This CAREER project will address critical knowledge gaps in understanding how surface topographies on biomaterials affect interactions between host immune cells and pathogens. Despite evidence suggesting that nanoscale and microscale surface patterns can modulate bacterial behavior and immune responses, their effects on host–pathogen interactions remain poorly understood. Using a bottom-up patterning approach, the research will generate a library of topographies with precisely tuned nano to microscale features to investigate how surface topography modulates host–pathogen dynamics. The central hypothesis is that precise spatial patterning of biomaterials can restore immune balance and enhance host defenses, thereby improving infection control. This hypothesis will be tested through two objectives: (1) elucidate how controlled 2D topographies affect the regulatory role of immune cells in controlling bacterial infections; and (2) analyze the impact of 3D topographical cues on cell responses to gain insights into the topography–host–pathogen interactions in extracellular matrix-like 3D environments. To achieve this, versatile 3D patterning tools will be developed by incorporating 3D elements into the fabrication process, enabling precise patterning across various scales and geometries. Fundamental insights gained on interactions between biomaterial topography, the host, and bacteria will facilitate the rational design of immune-instructive biomaterials, ultimately leading to effective strategies to combat implant infections and improve patient outcomes. 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.