Injury to tissue caused by device penetration of the skin triggers formation of extracellular traps.

Continuous glucose monitoring (CGM) systems are vital for diabetes management, but sensor performance is often compromised by host immune responses following insertion. This study investigates early tissue and immune reactions, focusing on neutrophil extracellular trap (NET) formation, or NETosis. In porcine models, insertion trauma rapidly induced NETosis, preceding vascular regression and fibrotic encapsulation-processes that may hinder glucose diffusion and impair sensor accuracy. In a murine air pouch model, sensor implantation elevated inflammatory cytokines (IL-6, KC/GRO) and neutrophil infiltration within 24 hours. Scanning electron microscopy revealed NETs exclusively in traumatized tissue. Notably, neutrophils from type 2 diabetes patients failed to undergo NETosis on polyurethane surfaces in vitro, suggesting impaired immune responses due to metabolic dysfunction. These findings identify NETosis as a key driver of early sensor-tissue interactions. Strategies to reduce insertion trauma and modulate NET formation may enhance CGM reliability and longevity, informing future improvements in sensor design and deployment.