Abstract
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.
Highlights
Multi-contact cuffs are often used for selective recording and stimulation from individual nerve fascicles innervating different muscle targets[15,16,17]
We previously suggested the use of thiol-ene/acrylate based shape memory polymers (SMP) for neural interfaces, as they can be photolithographically processed in thin films (5–50 μm) for the fabrication of neural devices designed for various targets, including cortical probes, spinal cord stimulators, and nerve cuffs[22,23,24,25]
We report the fabrication of thin film cuff electrodes with photolithographically patterned Au and titanium nitride (TiN) contacts on a softening thiol-ene/acrylate polymeric substrate that fit snugly around peripheral nerves, allowing sensitive recording and selective stimulation with minimal fibrotic response over 30 days of implantation
Summary
Multi-contact cuffs are often used for selective recording and stimulation from individual nerve fascicles innervating different muscle targets[15,16,17]. High-resolution photolithographic fabrication of thin and flexible electrodes using ribbon-like materials such as polyimide have been reported[19], yet this polymer is relatively rigid (2.5 GPa), and cuffs made of this material bear the risk of nerve damage and inflammation This has motivated the development of hydrogel and nanofiber coatings onto polyimides to provide a softer interface, which complicates device manufacturing[20,21]. Several designs of Au and titanium nitride (TiN) multi-electrodes were fabricated and tested to show electrochemical performance and functionality in vitro, and to demonstrate acute and sub-chronic recording and stimulation of the rat sciatic and pelvic nerves (1–1.5 mm and 200 μm diameter, respectively) These multi-electrode softening cuff (MSC) devices were used to evoke monopolar and bipolar selective stimulation of the gastrocnemius and tibialis anterior muscles in the hind limb, from a cuff implanted in the sciatic nerve. We provide immunohistochemical evidence of reduced foreign body response by the SMP devices, compared to silicone nerve cuffs implanted side-by-side in the rat sciatic nerve for 30 days
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