The Effect of Local Subcutaneous Delivery of Vascular Endothelial Growth Factor on the Function of a Chronically Implanted Amperometric Glucose Sensor

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Abstract
The foreign body capsule that forms around implanted devices such as glucose sensors is hypovascular and has limited permeability to glucose. Such a capsule may function better if well vascularized. We hypothesized that capsular vascularization achieved by local release of vascular endothelial growth factor (VEGF) would lead to enhanced function. Amperometric glucose sensor array disks, each with four indicating electrodes, were implanted into rats. Animals received local subcutaneous infusions of VEGF165 via osmotic pumps at a location on the sensor face 2 mm from one of the electrodes ("near units"). "Intermediate" electrode units were 15 mm, and "distant" units were 22 mm, from the VEGF source. Every 2 weeks, a glucose infusion was given to assess sensor function by telemetry. Near units demonstrated a lower lag duration (delay after blood glucose) than intermediate and distant units. The mean absolute relative difference for near units was less than for distant units. The percentage of data pairs in the A region of the Clarke error grid of the near sensing units was greater than that of the distant units. Values for the functional measures for saline controls fell between near and distant VEGF values. Glucose sensor function was found to be more favorable in units immediately adjacent to the VEGF infusion port. The most likely cause for this finding is increased neovessel growth in the surrounding foreign body capsule. Slow release of angiogenic growth factors may be a potential method for chronically enhancing the function of a subcutaneously implanted biosensor.