NL1036784C2 - A three-dimensional bifurcating micro-channel construct for regenerative bidirectional neuro-electric interfacing. - Google Patents

Description

A three-dimensional bifurcating micro-channel construct for regenerative bidirectional neuro-electric interfacing

SUMMARY OF INVENTION

5 The following describes a proposed implantable biomedical device that establishes bi-directional communication between the human peripheral nervous system (PNS) and a neuroprosthesis. This provides a user with intuitive control over, and feedback from, a prosthetic device, effectively replacing the lost function which the prosthesis replaces. This approach is particularly suited when trying to effectively interface with a PNS fascicle containing ‘mixed’ neurons, meaning both 10 afferent (sensory) and efferent (motor) neurons.

The neurons of the PNS are known to regenerate into surrounding tissue of the amputation site, attempting to find appropriate target tissue to innervate. They do so in a bundling manner, making it difficult to differentiate individual neurons and associated action potentials.

15

Figure 1 shows one representation of the intended device, which takes the form of a biocompatible polymer end cap (1) which is fitted over the end of a recently severed fascicle (3) of the PNS. The end cap provides an alternative extracellular environment of micro-channels (4) into which neurons (5) can regenerate in a controlled manner.

20

Figure 2 represents a formation of the micro-channel networks shown in Figure 1. The round microchannels (4) initially begin large (approximately 100 pm diameter) to encourage neural ingrowth into the device. These channels proceed through a series of bifurcations (10), becoming progressively smaller with each division (down to 2.5 pm in diameter) such that ingrowing neurons 25 are encouraged to separate from one another with the eventual goal that single neurons populate single micro-channels.

The micro-channels guide these individual neurons toward micro-well chambers (6) containing appropriate innervation target tissue (7). This is required to ensure the long term survival of 30 ingrowing neurons. The innervation target tissue can consist of either a pre-cultured neural probe of intemeurons or of pre-cultured smooth muscle. Electrical contact is made with the neurons either via electrodes placed within the micro-channels (8) en route to the micro-well chambers, taking 1036784 2 advantage of single amplification of action potentials that occurs within a micro-channel, or through electrodes located within the micro-well (9), using the target tissue as the intermediate signal interface and possible signal amplifier.

5 The final proposal is to achieve a one-to-one relationship between electrodes and neurons within a fascicle - or as close as possible to a one-to-one mapping. This device effectively separates out the constituent parts of a fascicle and establishes a strong, stable and long-term contact with each separate neuron. It allows for improved ‘graded’ motor responses of a neuroprosthesis based on the activation of more and more neurons, which is easily measured with this device as more electrode 10 sites become active. Also, in the case of a sensory neuron, total sensory response can be restored as each neuron associated with a specific sensory role can be reassigned accordingly to accept signals from an equivalent sensing mechanism in the neuroprosthetic device.

The micro-channel walls can be coated with a biocompatible polymer. This reduces the size of the 15 micro-channels, thus encouraging a greater degree of separation via volume limitation and also provides a medium for bioactivation via the integration of appropriate biomolecules within the polymer matrix.

To further promote neural ingrowth, the micro-channels can be seeded with Schwann cells to further 20 enhance the recreation of the endoneurial tubes into which neurons regenerate into in the optimal natural setting. A bifurcating pattern of linear groove microstructures may also be incorporated on the surface of the micro-channels, mimicking the fine longitudinal collagen structures lining the endoneurial tubes. These can be placed before each micro-channel bifurcation in a diverging pattern to further encourage neuron separation.

25 1036784

Claims (7)

An implantable peripheral neural interface for both recording nerve signals and for nerve stimulation, with high selectivity regarding the splitting of nerve bundles 5 (fascicles) into individual nerve fibers (neurites), comprising the device: - A nerve cuff (2) for confirming the proximal nerve stump or nerve fascicle (3). - A cap (1) at the end of the nerve cuff, containing several microchannels (4) in which neurites (5) can grow. 10. Micro channels (4) ending in wells (6) filled with target tissue (7) - Electrodes (8) in the micro channels and electrodes (9) in the wells to directly or indirectly (via muscle cells) the two-way communication with the ingrowing neurites to take care of. The device of claim 1, including microchannels (4) that repeatedly split (10), to promote separation of the ingrowing bundle of neurites (11) into individual smaller bundles (12), to eventually separate into individual neurites. The device of claim 2, including microchannels (4) which traverses a sufficient number of splices (10) to isolate separate neurites (13), the microchannels ending in pits (6). The device of claim 3, including microchannels (4) that decrease in size at each cleavage to effect the separation of the neurite bundle. 25 The device of claim 4, with linear, diverging microstructures disposed therein from each split (10) to further promote separation. 6. The device of claim 5, wherein specific use is made of smooth muscle cells or smooth muscle tissue as target tissue (7) in wells (6), for both sensory and motor neurons. 1036784 The device of claim 6, wherein the walls of the microchannels (4) are covered with a bio-polymer. 1036784