(K-424) Electrochemical Analysis of Bioabsorbable Peripheral Nerve Stimulator Devices

Chronic pain affects around 20% of adults in the United States [1]. Opioids are the main form of treatment. However, due to the opioid crisis, the demand for non-pharmacological alternative methods of chronic pain relief has increased. One effective treatment is peripheral nerve stimulation (PNS). While the exact mechanism is unknown, a proposed theory is “gated transmission”. 100Hz stimulation delivered near the nerve selectively activates large sensory fibers. This activation is thought to compete with the pain signals being sent by smaller nociceptive fibers effectively reducing their transmission [2]. 

 Among different PNS strategies, temporary percutaneous PNS devices composed of wired electrode, typically made of stainless steel, and connected to an external controller that provides the stimulation pulses. Temporary PNS treatment for 60 days has shown long-term pain relief even after the cessation of stimulation, offering a chronic pain solution without the use of addictive drugs [3]. 

Electrode removal by a physician is required after 60 days and the removal comes with a high percentage of lead breakage, leaving permanent material fragments inside the body. To address this, a completely bioresorbable electrode has been developed. The novel electrode contains a bioabsorbable metal wire insulated with a degradable polymer. This allows the electrode to detach from the external controller and degrade within the body, eliminating the need for removal. The device also includes a degradation-on-command (DOC) feature that accelerates metal degradation once PNS treatment is completed. Here, we evaluate the electrochemical properties of the electrode using invitro accelerated aging and electrical stimulation.

The bioabsorbable electrodes used were made by a multi-stranded wire of degradable metal (diameter ~200 um) and insulated with a bioabsorbable polymer via dip coating. For the aging study, electrodes were fully insulated. For the stimulation study, 1cm of the wire was de-insulated at the tip. 

To observe the electrical properties of the insulation during aging, the electrodes were incubated in artificial cerebral spinal fluid (aCSF) at 60°C. Samples tubes were sealed to prevent evapotation of aCSF. The impedance through the insulation was measured weekly using electrochemical impedance spectroscopy (EIS).  

For the stimulation study, we compared the impact of the therapeutic stimulation (biphasic square wave at 100Hz) and the DOC stimulation (anodic monophasic, >50% duty cycle) in aCSF at 37°C. A non-stimulated wire was used as a negative control. EIS measurements and samples of the aCSF were taken hourly over 3hrs of stimulation to track degradation. The metallic ion release rate was quantified from the aCSF samples using a colorimetric light absorbance assay. This also allows us to measure the maximum dose of metallic ions released when the electrode is fully degraded via DOC.  

For the aging study, the impedance of the electrodes shows a decreasing trend over time (Figure 1A). This indicates that the insulation is successfully degrading under accelerated aging conditions. This will inform future stability testing so that we can tune the insulation to be stable during treatment but degrade afterwards. 

For the stimulation study, the impedance of the DOC electrode shows a slight decrease of about 20Ω at 100Hz during the first hour of stimulation (Figure 1B). After the slight decrease, the impedance during DOC stimulation increased by two orders of magnitude (10kΩ) over the next two hours until the wire was significantly degraded. This sharp increase is likely due to portions of the wire detaching as the degradation progresses. The electrode undergoing biphasic stimulation had a similar decrease in impedance as the DOC electrode (about 45Ω) in the first hour. Stimulations may cause slight delamination of the insulation or slight roughening of the electrode surface, resulting in increased surface area, thus, decreased impedance. As stimulation continued, the impedance increased slightly to return to baseline. This demonstrates that the electrode is electrochemically stable during therapeutic stimulation. The impedance of the non-stimulated electrode increased from ~160Ω to ~420Ω over the course of 3hrs. This suggests there may be non-conductive metal oxides forming on the electrode surface during passive incubation. 

Metallic ion release was 0.06-1.5µg/hr for the biphasic stimulation and non-stimulated condition (Figure 1C). This suggests that the biphasic stimulation is not causing increased metal release. During DOC stimulation, about 65µg were released within the first hour, and about 14-40µg/hr were released afterward. This demonstrates that the DOC stimulation causes the greatest metal ion release within the first hour of stimulation. Overall, these results demonstrate that the Vanish electrode can provide therapeutic stimulation while also being degradable in vitro. Future studies will include evaluation of the degradable electrode in vivo using rodent models.  

[1] 

J. Dahlhamer et al., “Prevalence of Chronic Pain and High-Impact Chronic Pain Among Adults — United States, 2016,” MMWR. Morbidity and Mortality Weekly Report, vol. 67, no. 36, pp. 1001–1006, Sep. 2018, doi: https://doi.org/10.15585/mmwr.mm6736a2. 

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[2] 

S. Helm et al., “Peripheral Nerve Stimulation for Chronic Pain: A Systematic Review of Effectiveness and Safety,” Pain and Therapy, vol. 10, no. 2, pp. 985–1002, Sep. 2021, doi: https://doi.org/10.1007/s40122-021-00306-4. 

[3] 

C. A. Gilmore et al., “Percutaneous 60-day peripheral nerve stimulation implant provides sustained relief of chronic pain following amputation: 12-month follow-up of a randomized, double-blind, placebo-controlled trial,” Regional Anesthesia & Pain Medicine, vol. 45, no. 1, pp. 44–51, Nov. 2019, doi: https://doi.org/10.1136/rapm-2019-100937. 

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