Totally Organic Hydrogel-Based Self-Closing Cuff Electrode for Vagus Nerve Stimulation

Abstract

An intrinsically soft organic electrode consisting of poly(3,4-ethylenedioxythiophene)-modified polyurethane (PEDOT-PU) is embedded into a bilayer film of polyvinyl alcohol (PVA) hydrogels for developing a self-closing cuff electrode for neuromodulation. The curled form of the PVA hydrogel is prepared by releasing internal stress in the bilayer structure. The inner diameter of the cuff electrode is set to less than 2 mm for immobilization to the vagus nerve (VN) of humans and pigs. The stability of the immobilization is examined, while the pressure applied to a nerve bundle is at a harmless level (≈200 Pa). Since the electrode is totally organic, MRI measurements can be conducted without image artifacts. The large electric capacitance of the PEDOT-PU (≈27 mF cm^-2 ) ensures a safe stimulation of living tissues without Faradaic reactions. The practical performance of the cuff electrode for VN stimulation is demonstrated by observation of bradycardia induction in a pig.

Keywords: MRI compatible implants; cuff electrodes; hydrogels; self-closing; vagus nerve stimulation.

Figure 1

Schematic of a hydrogel‐based self‐closing cuff electrode, which can be spontaneously immobilized to a nerve bundle: a) opening and attaching the cuff electrode to a nerve bundle; b) self‐closing of the electrode; c) immobilization to the nerve bundle by wrapping.

Figure 2

a) Left: the electrical resistance of a PEDOT‐PU film and of its laminate. The data represent the averaged resistance (n = 3 individual tests). Right: image of the single PEDOT‐PU film and lamination with uniform rolling pressure. b) Typical cyclic voltammogram of the Pt of commercial cuff electrode and the PEDOT‐PU electrode (laminate of three films). c) Typical AC impedance spectra of the Pt electrode and the PEDOT‐PU electrode.

Figure 3

a) Left: fabrication process of the curled PVA hydrogel bilayers and images of typical samples formed from various thickness of PVA hydrogel layers (200, 500 and 1000 µm) at 1.5 strain. As the definition of strain, a value of 1.0 is that layer 2 is stretched to twice its original length. Right: inner diameters of the curled PVA hydrogels prepared by changing the thickness of the PVA layers and the stain applied to layer 2. The data represent the mean ± standard error of the mean of inner diameter (n = 3 individual tests). b) Left: fabrication process of the PEDOT‐PU/PVA cuff electrode by sandwiching the PEDOT‐PU with the PVA layers. Right: sequential images of the PEDOT‐PU/PVA cuff electrode, which is wrapping around a 2 mm agarose hydrogel rod. The electrode was prepared by applying 1.5 strain to the 200 µm thick PVA films. c) Immobilization forces of the PVA hydrogel and the PEDOT‐PU/PVA cuff electrode wrapped around a 2 mm agarose hydrogel rod in the sliding direction (left) and wrapped around a 2 mm steel rod in the peeling direction (right). d) Average pressure induced by the PEDOT‐PU/PVA cuff electrode in saline solution, measured by a 2.0 mm diameter silicon tube sensor. The data represent the mean ± standard error of the mean of pressure (n = 3 individual tests).

Figure 4

a) Monitoring of voltage between the cuff electrodes wrapped around a 2 mm diameter agarose hydrogel rod upon the application of square wave current pulses of ± 0.25 mA at 30 and 1 Hz. The PEDOT‐PU/PVA cuff electrodes (red) and the conventional Pt/silicone cuff electrode (gray) were used. b) Images of the Pt/silicone and PEDOT‐PU/PVA cuff electrodes embedded in an agarose hydrogel, and the cross sections of their MRI images.

Figure 5

a) The schematic of the configuration of the electrodes and the measurement setup for pig VNS. b) Heart rate response during VNS with biphasic square wave pulses (500 µs width) of 3, 5, and 10 mA at a frequency of 30 Hz for 90 s (yellow area). c) The PEDOT‐PU/PVA cuff electrode wrapped around the cervical VN of a pig and a thermographic image around the PEDOT‐PU/PVA cuff electrode during VNS.