Toward a Chronic VNS Strategy for Obesity Treatment: Pilot Study on a PFA-Based Neural Interface in Diet-Induced Obese Rabbits

Abstract

Subdiaphragmatic vagus nerve stimulation (VNS) is being explored as a device-based option for obesity, but translation is limited by the lack of standardized implantation workflows and cuff electrodes that remain stable at the cuff–nerve interface in a moist in vivo environment. Here, we aimed to establish a bench-to–in vivo feasibility platform that integrates a microfabrication-compatible perfluoroalkoxy alkane (PFA) film cuff with a reproducible rabbit surgical procedure and sham-controlled evaluation. The cuff electrode was fabricated using MEMS-based processes and characterized on the bench (impedance/charge metrics), then implanted on the subdiaphragmatic vagus nerve in diet-induced obese rabbits assigned to sham or intermittent VNS at graded current levels (total n = 8; n = 2/group). Body weight was tracked as an exploratory outcome under variable delivered exposure. During the stimulation window, weight trajectories showed heterogeneous, non-monotonic patterns across current levels, with partial rebound after stimulation cessation. Gross inspection and hematoxylin and eosin (H&E) histology indicated preserved fascicular organization with a thin peri-neural fibrotic capsule, assessed qualitatively in this pilot cohort. Overall, these results support feasibility of reproducible subdiaphragmatic implantation and cuff–nerve interface operation and motivate powered studies with exposure-matched delivery logging and expanded metabolic and longitudinal endpoints. Clinical and Impact: This work de-risks translation of subdiaphragmatic VNS by combining a scalable PFA-based cuff electrode with a reproducible intermediate-sized animal implantation workflow and conservative charge-density operation. The platform enables the next step: powered, controlled studies that optimize dosing and add metabolic and longitudinal interface endpoints relevant to implantable obesity neuromodulation.