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Regenerative neural interfaces for neuroprosthetic applications

Xavier Navarro1* and Jaume Del Valle1
  • 1 Universitat Autonoma de Barcelona, Dept. Cell Biology, Physiology and Immunology, Spain

The effective applicability of advanced bionic systems, particularly hand prostheses and exoskeletons, for the replacement and substitution of lost human sensory-motor functions due to limb amputation or neural injuries demands the possibility of creating a natural and selective link between the nervous system of the user and the artificial device (Micera and Navarro 2009). Only in this way, new systems will be incorporated into the natural control strategies of the subject. In such applications, recording neural efferent signals coming from the central nervous system can be used for the control of motion of the mechanical prosthesis, thus trying to replicate the movements of the natural hand/limb, whereas sensory feedback from tactile and force sensors embedded in the prosthesis may be delivered to the user by stimulating afferent nerve fibers within the residual limb nerves. Such a bionic system might be felt by the user as actually replacing the lost or hypofunctional natural limb. A variety of neuroprostheses, developed to substitute or mimic sensory-motor functions in patients with neurological deficits, include interfacing the peripheral nervous system by means of electrodes that may allow nerve stimulation and neural signal recording. Peripheral nerve interfaces are of interest because of their reduced invasivity compared with central neural interfaces, and the possibility of delivering an appropriate bidirectional communication by means of a single device, since peripheral neves contain both motor and sensory fibers. Different types of electrodes have been developed to interface the PNS for different biomedical applications (Navarro et al 2005; Schultz and Kuiken 2011). Nerve electrodes can be classified into three main categories depending on nerve invasiveness: extraneural, intraneural and regenerative (see supplementary Figure 1). With increasing invasiveness of the implant, higher selectivity of interfacing individual nerve fibers may be reached, lower intensity of stimulation is needed and better signal recording is achieved as the interposition of tissue between the electrode and the axons is reduced. Extraneural electrodes, such as cuff and epineurial ones, provide simultaneous interface with many axons in the nerve, mostly in the outer fascicles, resulting in poor selectivity but with small risk of nerve damage. Intraneural electrodes, such as LIFE, TIME and USEA, inserted in the nerve may interface discrete groups of axons within a fascicle reaching very good selectivity but with higher risk of nerve damage. Indeed, experimental research has proved the suitability and biocompatibility of intraneural electrodes, leading to a few reports of their use in human amputees allowing to perform distinct hand movements under voluntary control, and providing sensory feedback from the hand prosthesis giving perception of joint position and object recognition (Dhillon et al 2005; Horch et al 2011; Rossini et al 2010; Raspopovic et al 2014). Regenerative electrodes, implanted between the cut stumps of a peripheral nerve, are envisioned to interface a high number of nerve fibers by using an array of contacts covered by the axons as they regrow over or within them, thus, making it possible to record action potentials from and to stimulate individual or small groups of axons. The most logical and challenging application of regenerative electrodes consists on interfacing the severed nerves of an amputee limb for a bidirectional interface with a feedback-controlled neuroprosthesis. The applicability of regenerative electrodes is, however, dependent upon the success of axonal regeneration through the electrode device, the possible secondary nerve damage induced by mechanical load or by constriction imposed by the electrode, the biocompatibility of the components, and the adequacy of electronic components to interface regenerated axons. From the first theoretical concept presented more than 40 years ago (Llinás et al 1973), evolving techniques and designs have been used in the construction of regenerative electrodes. With the incorporation of microelectronic technologies, regenerative sieve electrodes of small dimensions and high numbers of holes were made on silicon substrate (Kovacs et al 1994; Navarro et al 1996; Wallman et al 2001). Using multiple holes silicon arrays, axonal regeneration and neural activity recordings were reported in laboratory animals (Kovacs et al 1994; Navarro et al 1996; Bradley et al 1997; Mensinger et al 2000). However, experimental studies showed that silicon sieve electrodes constituted a physical barrier limiting the growth of regenerating axons and also induced frequent signs of constrictive axonopathy depending on the size of the holes. Polyimide-based electrodes were introduced later and tested in injured rat and cat nerves. Several studies demonstrated that polyimide-based electrodes are biocompatible, stable over months after in vivo implantation, and allow for better nerve regeneration than silicon electrodes (Navarro et al 1998; Ceballos et al 2002). Polyimide sieve electrodes allowed selective stimulation of and recording from small groups of regenerated fibers (Lago et al 2007; Panetsos et al 2008). However, extensive research done with these electrodes has raised some questions that still need to be solved. Several alternative designs have been proposed for improving the amount of axonal regeneration through non-obstructive regenerative multi-electrodes. A simple design inserted needle electrodes transversally in a nerve guide used to bridge the sectioned nerve. Initial studies in vivo showed that such electrode arrays allowed the recording of action potentials from as early as 8 days post-implantation to as long as 3 months in a low proportion of the animals (Garde et al 2009). Recent alternatives of regenerative electrodes have explored the design of regenerative scaffolds (Clements et al 2013) and of microchannel electrodes (Lacour et al 2010). These electrodes could be thought as an evolution of sieve electrodes in which, instead of growing through holes, the axons grow via narrow parallel channels with embedded electrodes. The long contacts along the microchannel facilitate increasing the amplitude of recorded action potentials and allowing stimulation of a few axons with lower thresholds than with other types of electrodes (FitzGerald et al 2012). Some studies in rats reported that these new approaches allow high selectivity in recording and stimulation of the regenerated axons, although successful regeneration occurred only in a low proportion of the animals. New proposals, such as that of the MERIDIAN project, involve a hybrid regenerative device, which combines scaffold to guide regenerating axons, guidance cues to promote separate growth of selected axonal populations, and planar electrodes with multiple nano-contacts to increase the options for selective interfacing injured nerves.

Figure 1
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Acknowledgements

Financial support by the FP7-NMP "MERIDIAN" project, contract n. 280778-02.

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Keywords: Nerve Regeneration, Neuroprosthesis, peripheral nerve, regenerative electrode, sieve electrode

Conference: MERIDIAN 30M Workshop, Brixen, Italy, 25 Sep - 25 Sep, 2014.

Presentation Type: Oral Presentation

Topic: Neuroengineering

Citation: Navarro X and Del Valle J (2014). Regenerative neural interfaces for neuroprosthetic applications. Front. Neuroeng. Conference Abstract: MERIDIAN 30M Workshop. doi: 10.3389/conf.fneng.2014.11.00003

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Received: 06 Nov 2014; Published Online: 06 Nov 2014.

* Correspondence: Dr. Xavier Navarro, Universitat Autonoma de Barcelona, Dept. Cell Biology, Physiology and Immunology, Bellaterra, 08193, Spain, xavier.navarro@uab.cat