NeuroStitch: Nanofabrication of a High Resolution Biomimetic Peripheral Nerve Interface
Zeshaan N Maan, MD, MSc1, Eric T Zhao, MA1, Janos A Barrera, MD1, Dominic Henn, M.D.1, Jagannath Padmanabhan, PhD1, Kellen N Chen, PhD1, Nicholas T Melosh, PhD1 and Geoffrey C. Gurtner, MD2, (1)Stanford University, Stanford, CA, (2)Plastic and Reconstructive Surgery, Stanford University, Stanford, CA
Introduction:
Over half a million Americans living with an upper extremity amputation. These devastating injuries result in a loss of function and autonomy. Existing 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. Existing neural interfaces either lack the necessary selectivity and spatial resolution or are fragile, lack spatial selectivity, and ultimately fail due to the progressive fibrotic encapsulation of 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. Recent advances in semiconductor processing permit fabrication of biomimetic electrodes that are the same size as natural axons, minimizing mechanical mismatch and thereby foreign body reaction.
Methods:
Ultra-small and flexible electrodes of the same dimensions, compliance and spatial distribution as human axons were created using techniques employed for microprocessor fabrication. A 'needle and thread' approach, pulling the electrodes through the nerve, was used to implant the ultra-flexible devices, allowing the electrodes to interface directly with individual axons. Using histology, 2-photon imaging, and the Sciatic Functional Index (SFI), we assessed the neural injury associated with the device in a C57/BL6 mouse. We tested NeuroStitch function by stimulating the nerve with a positive and negative charge of 50 nanoColoumb per pulse. The Intan system was used to stimulate and record.
Results:
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 to baseline by 2 weeks post-implantation. Sparse action potentials were recorded within 30 minutes of device insertion. The ultra-small size of the electrodes and their proximity to individual axons permitted extremely local stimulation — down to a single toe.
Conclusions:
We demonstrate the ability to fabricate and insert biomimetic intraneural electrodes with minimal and recoverable nerve injury. The Neurostitch is capable of single neuron recording and high selectivity stimulation. 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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