Platinized graphene fiber electrodes uncover direct spleen-vagus communication.

Neural interfacing nerve fascicles along the splenic neurovascular plexus (SNVP) is needed to better understand the spleen physiology, and for selective neuromodulation of this major organ. However, their small size and anatomical location have proven to be a significant challenge. Here, we use a reduced liquid crystalline graphene oxide (rGO) fiber coated with platinum (Pt) as a super-flexible suture-like electrode to interface multiple SNVP. The Pt-rGO fibers work as a handover knot electrodes over the small SNVP, allowing sensitive recording from four splenic nerve terminal branches (SN 1-4), to uncover differential activity and axon composition among them. Here, the asymmetric defasciculation of the SN branches is revealed by electron microscopy, and the functional compartmentalization in spleen innervation is evidenced in response to hypoxia and pharmacological modulation of mean arterial pressure. We demonstrate that electrical stimulation of cervical and sub-diaphragmatic vagus nerve (VN), evokes activity in a subset of SN terminal branches, providing evidence for a direct VN control over the spleen. This notion is supported by adenoviral tract-tracing of SN branches, revealing an unconventional direct brain-spleen projection. High-performance Pt-rGO fiber electrodes, may be used for the fine neural modulation of other small neurovascular plexus at the point of entry of major organs as a bioelectronic medical alternative.

Intraneural ultramicroelectrode arrays for function-specific interfacing to the vagus nerve.

Selective interfacing to small multifunctional nerves such as the vagus nerve (VN) which is the main multimodal autonomic nerve that provides a major communication pathway from vital peripheral organs to the brain, can have significant potential in treating and diagnosing diseases as well as enhancing our understanding of peripheral nerve circuits. Here we describe the fabrication of a 16-channel intraneural electrode array with ultramicro-dimensioned electrodes to achieve improved functionally selective recording. We demonstrate that the amorphous silicon carbide ultramicroelectrode arrays (a-SiC UMEAs) provide selectivity in the detection of neural activity in the cVN related to changes in systemic oxygenation and blood pressure. We will also demonstrate spatially selective recording of micro-compound action potentials (µCAPs) by electrical stimulation of the subdiaphragmatic branches of the VN. Distinct neural activity was recorded on electrodes separated by less than about 100 µm. This is the first time that this level of spatially selectivity recording has been demonstrated in the cVN with an intraneural multielectrode array.

Thin Film Multi-Electrode Softening Cuffs for Selective Neuromodulation.

Silicone nerve cuff electrodes are commonly implanted on relatively large and accessible somatic nerves as peripheral neural interfaces. While these cuff electrodes are soft (1-50 MPa), their self-closing mechanism requires of thick walls (200-600 µm), which in turn contribute to fibrotic tissue growth around and inside the device, compromising the neural interface. We report the use of thiol-ene/acrylate shape memory polymer (SMP) for the fabrication of thin film multi-electrode softening cuffs (MSC). We fabricated multi-size MSC with eight titanium nitride (TiN) electrodes ranging from 1.35 to 13.95 × 10-4 cm2 (1-3 kΩ) and eight smaller gold (Au) electrodes (3.3 × 10-5 cm2; 750 kΩ), that soften at physiological conditions to a modulus of 550 MPa. While the SMP material is not as soft as silicone, the flexural forces of the SMP cuff are about 70-700 times lower in the MSC devices due to the 30 µm thick film compared to the 600 µm thick walls of the silicone cuffs. We demonstrated the efficacy of the MSC to record neural signals from rat sciatic and pelvic nerves (1000 µm and 200 µm diameter, respectively), and the selective fascicular stimulation by current steering. When implanted side-by-side and histologically compared 30 days thereafter, the MSC devices showed significantly less inflammation, indicated by a 70-80% reduction in ED1 positive macrophages, and 54-56% less fibrotic vimentin immunoreactivity. Together, the data supports the use of MSC as compliant and adaptable technology for the interfacing of somatic and autonomic peripheral nerves.