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