Neuro-stitch: Nanofabrication Of A Biomimetic Peripheral Nerve Interface
Zeshaan N. Maan, MD, MSc1, Eric T. Zhao, MS2, Janos Barrera, MD1, Jagannath Padmanabhan1, Dominic Henn, MD1, Kellen Chen, PhD1, Clark A. Bonham, BA1, Nicholas Melosh, PhD2, Geoffrey C. C. Gurtner, MD1.
1Stanford University School of Medicine, Stanford, CA, USA, 2Stanford University School of Engineering, Stanford, CA, USA.
Approximately 185,000 people suffer limb loss annually in the United States (one million worldwide), with over half a million Americans living with an upper extremity amputation, the vast majority of whom are young and otherwise healthy. These devastating injuries result in a loss of function and autonomy. Existing functional prostheses are cumbersome and tiring, with a limited capacity to recapitulate natural hand motion, which requires a stable, high fidelity neural interface for 2-way communication between robotic prostheses and the patient’s neural circuitry. Extraneural cuff electrodes lack the necessary selectivity and spatial resolution, while intraneural electrodes, such as the Utah Slanted Electrode Array (USEA) and Transverse Intrafascicular Multichannel Electrode (TIME), are fragile, lack spatial selectivity, and ultimately fail from a progressive fibrotic encapsulation due to a foreign body response (FBR). “Regenerative peripheral neural interfaces” (RPNIs) employ denervated muscle to avoid direct nerve/electrode interactions, but require surgical creation and still suffer from limited spatial resolution. Interestingly, recent developments in brain machine interfaces have demonstrated that designing electrodes mimicking the size and compliance of native tissue, minimizing mechanical mismatch, reduces foreign body reaction.
We employed nanofabrication techniques, typically used for microprocessor creation, to create ultra-small, flexible electrodes of the same dimensions, compliance and spatial distribution as human axons. We overcome the major roadblock of implantation of ultra-flexible devices using a ‘needle and thread’ approach, pulling the electrodes through the nerve stump to allow the electrodes to interface directly with individual axons. We use histology and 2-photon imaging to assess intraneural distribution in the sciatic nerve of a C57/BL6 mouse. We use sciatic functional index (SFI) to assess neural injury as a consequence of insertion. We tested NeuroStitch function by stimulating the nerve with a positive and negative charge of 50 nanoColoumb per pulse.
We successfully fabricated a biomimetic neural probe that is 4 micrometers wide and 2 micrometers thick, which makes it 150 times more compliant than TIME electrodes, and were able to insert it into a mouse sciatic nerve with a pull through approach using 11-0 suture. 2-photon imaging demonstrates the biomimetic size and distribution of individual electrodes within the nerve. SFI demonstrates resolution of the initial neuropraxia (-45 at day 1) to baseline at 2 weeks post surgery. Stimulation of the sciatic nerve with the Neurostitch results in contraction of specific muscles within the mouse hindlimb.
Our results demonstrate the feasibility of fabricating and inserting a biomimetic, ultra flexible electrode into a peripheral nerve with minimal acute damage that resolves. Additonally, our NeuroStitch device shows functionality in stimulating a peripheral nerve. This device represents a step forward in the development of a high resolution, stable man/machine interface for next generation neuroprostheses.
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