Neurophysiologic and Chronic Safety Testing of a Miniaturized Active Implanted Device with Integrated Electrodes for Bioelectronic Medicine Applications.

New dosing paradigms in bioelectronic medicine applications, such as low duty cycle stimulation of the vagus nerve to treat inflammatory disorders, enable architectural shifts in active implantable devices that benefit patients. Herein, we describe various features of the MicroRegulator (MR), an innovative neurostimulation system that includes a unique electrode-integrated implantable nerve stimulator. To verify efficient activation of neuronal targets within the vagus nerve, a geometric emulator of the MR (identical form and electrical contact properties as the clinical MR device) was tested in situ and neurophysiologic outcomes were compared to a control electrode in wide clinical use. The data demonstrated comparable patterns of compound potentials evoked from the MR emulator and the control electrode, with the MR emulator requiring a lower threshold current to depolarize the nerve. To verify chronic mechanical safety, the MR emulator was implanted for 2 months on the vagus nerves of canines. Blood flow through the major cervical vessels was unaffected, and pathologic and histologic findings included normal foreign body encapsulation and an absence of demyelination and nerve damage. Together these finding support the feasibility of the MR system for clinical translation.