Continuous glucose monitoring (CGM) using implantable glucose sensors is a critical tool in the management of diabetes. Unfortunately, current commercial glucose sensors have limited performance and lifespans in vivo, considered to be due to sensor-induced tissue reactions (inflammation, fibrosis, and vessel regression). Previously, our laboratory utilized monocyte/macrophage (Mo/MQ) deficient and depleted mice to establish a causal relationship between Mo/MQ accumulation and inflammation in glucose sensor performance in vivo. Using C-C chemokine ligand-2 (CCL2) and C-C chemokine receptor-2 (CCR2) knockout mice, we next established that deletion of this Mo/MQ chemokine family, suppressed inflammation at the sensor-tissue interface in these mice, while improving sensor performance over a 4-week post-sensor implantation, compared to normal mice. These studies underscore the importance of the CCL2 family of chemokines and receptors in Mo/MQ recruitment/activation, and sensor performance in vivo. In the present study, we systemically administered Bindarit, a CCL2 synthesis inhibitor, to assess the role of CCL2 chemokines, Mo/MQ recruitment and inflammation at sensor implantation sites, on CGM performance in vivo. These studies demonstrate that systemic administration of Bindarit substantially reduced sensor-induced inflammation, particularly MQ recruitment, preventing sensor biofouling in our CGM mouse model. These results not only confirm the major role monocytes/macrophages play, but directly demonstrate that CCL2 drives Mo/MQ recruitment and biofouling of glucose sensors in vivo. These findings support future studies incorporating Mo/MQ migration/chemotaxis inhibitors, like CCL2, on sensor coatings to improve glucose sensor accuracy and lifespan in vivo.
Keywords: CCL2; CGM; Diabetes; Inflammation; Macrophages; Sensors.