• polymeric cuff electrode
• PEDOT:PSS
• PDMS
• neural interface

Among the multitude of nerves constituting the autonomic nervous system, the vagus nerve (VN) emerges as the longest and most relevant nerve. It enables bidirectional communication between brain and body organs, for it is involved in the regulation of autonomic, cardiovascular, respiratory, gastrointestinal, immune, and endocrine systems. Given the multitude of organs, including the larynx, pharynx, heart, lungs, and gastrointestinal ones, linked to the VN through afferent and efferent pathways, a broad spectrum of pathologies can be associated with its dysfunction. Simultaneously, disorders affecting organs either directly or indirectly innervated by the VN can be targeted or mitigated through the strategic modulation of this nerve's activity. Electrical stimulation of the VN is an approved therapy for refractory epilepsy, treatment-resistant depression, obesity, and stroke rehabilitation, and it has also been tested, among other diseases, in heart failure, inflammatory bowel disease, and rheumatoid arthritis. Currently, though, systems for Vagus Nerve Stimulation (VNS) suffer from low specificity in fiber stimulation, which leads to side effects such as cough, throat pain, voice alteration, and dyspnea due to the unwanted activation of off-target motor efferent fibers innervating throat muscles. Therefore, innovative neural interfaces allowing for a more targeted stimulation of the nerve fibers are of particular interest in this field. In this regard, the proven organotopy of the vagus nerve makes multi-contact cuff electrodes particularly effective in providing a radially and functionally selective stimulation of this nerve. Besides, this kind of interface benefits from a reduced foreign body reaction, due to its low invasiveness, further diminished in the case of a well-designed anchoring strategy and properly selected soft and biocompatible materials.
The aim of this thesis was to establish a robust and low-cost fabrication protocol for manufacturing fully- polymeric multi-contact cuff electrodes. Specifically, electrodes were intended to be made entirely of Polydimethylsiloxane (PDMS) and a 5 wt% solution of poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) in a mixture of deionized water and dimethyl sulfoxide (DMSO) in an 80:20 ratio. The rationale behind the fully-polymeric approach was to avoid the metal-related issues of both the mechanical tissue-electrode mismatch, causing harsh Foreign Body Reactions (FBRs) and hence hindering long-term applications, and the potential triggering of redox processes, leading to the in situ release of metal ions. The initial premise was to create two layers of PDMS, each approximately 100 μm thick, with conductive PEDOT:PSS traces encapsulated in between. One of these layers, the one in contact with the nerve, had to feature some strategically placed active site holes to allow exposure of the conductive material. The electrode dimension was tailored to the swine VN (approximately 3 mm in diameter). Moreover, an innovative strategy for securely fastening the flat cuff electrode once wrapped around the nerve was devised. This strategy involved equipping one side of the electrode with a belt loop-shaped hole while incorporating a locking geometry on the opposite end.
To this extent, an innovative fabrication strategy was developed after testing an extrusion printing approach. The specifics of this fabrication strategy are not disclosed as they are the subject of a patent submission. With our methodology, an electrode prototype was manufactured and subjected to optical and electrochemical testing. The electrochemical tests involved Electrochemical Impedance Spectroscopy (EIS) and Cyclic Voltammetry (CV).
The produced electrode featured conductive traces and active sites with an average width of 206 ± 26 μm, and 293 ± 25 μm, respectively, and fitted a 2740 µm diameter circle when wrapped and secured with the custom locking mechanism. The EIS resulted in the assessment of an average active site impedance at 1 kHz of 4.28 ± 2.93 kΩ, excluding an outlier active site. The CV enabled the calculation of the cathodic charge storage capacity, averaging 6022 ± 1208 mC/cm^2. Furthermore, the absence of peaks in the CV plots of the measured cathodic current over the normalized potential, aside from the broad anodic and cathodic ones at the ends of the scanned range, was considered an indicator of electrochemical stability and the absence of potentially detrimental redox processes.