Morphologic and functional evaluation of peripheral nerve fibers regenerated through polyimide sieve electrodes over long‐term implantation

Abstract

We evaluated by morphologic and functional analysis the regeneration of peripheral nerve fibers through polyimide regenerative-type electrodes over long-term implantation. Polyimide sieve electrodes were placed in silicone chambers and implanted between the severed ends of the sciatic nerve in rats. The sieve part had 281 round via holes of 40 microm in diameter, with nine integrated recording-stimulating electrodes arranged around the via holes. The degree of axonal regeneration was examined at 2, 7, and 12 months postimplantation (mpi). Regeneration was successful in 12 of the 13 animals implanted. Reinnervation of distal muscle and nerves increased with time, reaching a plateau about 7 mpi. The number of myelinated fibers increased from 2 to 7 months, at which time it was similar to control values. With time the myelinated fibers matured, with significant increases in axon diameter and myelin thickness. Only 0.6% of the regenerated axons showed evidence of compression near the implanted electrode. The majority of the myelinated fibers that crossed the via holes and had been regenerated through the distal nerve had a normal appearance. Sieve electrodes were useful for nerve stimulation at postimplantation. Stimulation through different active electrodes excited nerve bundles, evoking compound muscle action potentials of varying shape and amplitude, indicative of selective axonal stimulation.

Differences Exist in the Left and Right Sciatic Nerves of Naïve Rats and Cats

“…Specifically, the sciatic nerve is the peripheral nerve of choice when conducting animal studies involving nerve gap repair or peripheral nerve electrode implantation. With regard to electrode implantation, the rat sciatic nerve has been used extensively in experiments with nerve cuff (Jellema and Teepen, 1995;Rodrıguez et al, 2000;Vince et al, 2004;Vince et al, 2005a,b) and sieve or regenerating electrodes (Klinge et al, 2001;Ceballos et al, 2002;Lago et al, 2005;Castro et al, 2008;Kim et al, 2009;Lacour et al, 2009), whereas the cat sciatic nerve is also commonly used in nerve cuff electrode studies (Stein et al, 1977;Hoffer et al, 1981;Krarup and Loeb, 1988;Walter et al, 1995;Loeb and Peck, 1996;Grill and Mortimer, 2000;Romero et al, 2001) and has been used more frequently for experiments using penetrating peripheral nerve devices (Branner et al, 2001(Branner et al, , 2004Leventhal et al, 2006). To understand the changes that might occur in the underlying nerve after the implantation of these peripheral nerve devices, it is necessary to have knowledge of the basic structure and composition of the nerve under normal conditions.…”

“…The composition of the rat sciatic nerve has been relatively well studied and morphometric parameters for myelinated fibers, such as fascicle area (Podhajsky and Myers, 1993;Di Benedetto et al, 1998), fiber count (Jenq and Coggeshall, 1985a,b;Jenq et al, 1986;Schmalbruch, 1986;Rodrıguez et al, 2000;Ceballos et al, 2002;Rafiuddin Ahmed and Jayakumar, 2003;Lago et al, 2005Lago et al, , 2007Prodanov and Feirabend, 2007), fiber density (number of myelinated fibers per fascicle unit area) (De Angelis et al, 1994;Rodrıguez et al, 2000;Mazzer et al, 2008), fiber packing (the percent of the fascicular area occupied by myelinated fibers) (Koller et al, 1992), mean fiber diameter (Le Beau et al, 1988;Koller et al, 1992;De Angelis et al, 1994;Di Benedetto et al, 1998;Prodanov and Feirabend, 2007), fiber diameter distributions (Strain and Olson, 1975;Schmalbruch, 1986;Wehling et al, 1992;Rodrıguez et al, 2000;Prodanov and Feirabend, 2007;Mazzer et al, 2008), and mean g-ratio (Adhami et al, 1976;De Angelis et al, 1994;Di Benedetto et al, 1998;Rodrıguez et al, 2000;Rafiuddin Ahmed and Jayakumar, 2003;Mazzer et al, 2008) or g-ratio distributions (Mazzer et al, 2008), have been described (Table 1). It is important to recognize that such data have been collected from multiple strains and from rats of varying ages, variables whose influence on morphometric parameters have not been exami...…”

Restoration of Movement by Implantable Neural Motor Prostheses

“…A feature of silicon is that the circuitry to process recorded signals and apply multiplexing can be made as an integral part of the device. An example where sieves having 30-mm-holes and 30% transparency (ratio of open space versus closed area of the sieve) yielded to the best nerve regeneration [38% of functional gastrocnemeus electromyography (EMG) in a rat sciatic model] was presented by Ceballos et al [14]. Sieve electrodes have not yet been tested in human applications.…”

“…4 in [33].) 14.5 CLINICAL APPLICATIONS: EXAMPLES mechanisms when, for example, lifting an object in a precision grip. The fingers of the human hand are subserved by an estimated 200-300 touch-sensing receptors per square centimeter within the skin.…”

Handcrafted Microwire Regenerative Peripheral Nerve Interfaces with Wireless Neural Recording and Stimulation Capabilities

“…The peripheral nerve has been one target for bidirectional interfacing, with renewed interest generated by reports that peripheral nerve tissue is viable for interfacing even years after injury or amputation [1][2][3][4]. Several designs, such as cuff electrodes, flat interface nerve electrodes (FINE) [5][6][7], longitudinal intrafascicular electrodes (LIFE) [5, [8][9][10], Utah Slanted Electrode Arrays (USEA) [11][12][13], and regenerative sieve and microchannel electrodes [14][15][16][17][18][19][20] demonstrated selective recording and stimulation. However, the devices have limited electrode sites and recordings can only be obtained from the limited number of nerve fascicles.…”