Device Insertion Versus Material: Drivers of Inflammation in Diabetes Device Interfaces

Automated insulin delivery (AID) systems are limited by the short wear time of insulin infusion sets, which typically need replacement every 2 to 3 days, significantly shorter than the 14-day lifespan of continuous glucose monitoring (CGM) sensors. Infusion set failure remains a major obstacle to AID reliability and patient adherence. This study examined the roles of insertion trauma and biomaterial composition in causing acute inflammatory responses using both swine and mouse models.

We evaluated three commercial CGM sensors (Abbott Libre 2, Dexcom G7, Medtronic Guardian 3) and two Teflon-based IIS catheters (Medtronic QuickSet and i-Port Advance). In swine, tissue was histologically analyzed one day after implantation to assess neutrophil extracellular trap (NET) formation. In a murine air pouch model, we isolated material-specific immune responses by reducing mechanical injury. Lavage fluids collected at 1 and 3 days postimplantation were examined for immune cell infiltration and cytokine expression using flow cytometry and MSD multiplex assays.

NETs were observed at all insertion sites, indicating that tissue trauma, rather than the material itself, is the primary trigger of early NET formation. However, Teflon catheters caused a more prolonged inflammatory response, with increased recruitment of macrophages and mast cells, and higher levels of TNF-α and KC/GRO. In contrast, polyurethane-based sensors induced minimal immune activation, suggesting greater biocompatibility. The findings were consistent across models, although some species-specific differences were noted.

These findings underscore the importance of minimizing insertion trauma and selecting biocompatible materials to promote device-tissue integration, prolong wear time, and enhance AID system performance.