In vitro Verification of a 3-D Regenerative Neural Interface Design: Examination of Neurite Growth and Electrical Properties Within a Bifurcating Microchannel Structure

Abstract

| Toward the development of neuroprosthesis, we propose a 3-D regenerative neural interface design for connecting with the peripheral nervous system. This approach relies on bifurcating microstructures to achieve defasciculated ingrowth patterns and, consequently, high selectivity. In vitro studies were performed to validate this design by showing that fasciculation during nerve regeneration can be influenced by providing a scaffold to guide growth appropriately. With this approach, neurites can be separated from one another and guided toward specific electrode sites to create a highly selective interface. The neurite separation characteristics were examined for smaller microchannel structures (2.5 and 5 m wide) and larger microchannels (10 and 20 m wide), with smaller microchannels shown to be statistically more effective at initiating separation. Electrodes incorporated at different locations within the microchannels allowed for the recording and tracking of action potential propagation. Microchannel size was also found to play an important role in this regard, with smaller microchannels amplifying the recordable extracellular signal; a twofold increase in the signal to noise ratio was found for 5 m wide microchannels.

Functional recordings from awake, behaving rodents through a microchannel based regenerative neural interface

“…However, leveraging the amplifying properties of microchannels must also be balanced with design characteristics to optimize axon ingrowth and regeneration into microchannels. Although in vitro results disagree on the optimal microchannel caliber to promote sustained axon ingrowth, in vivo experiments, demonstrating fibrous sheath micro-fascicular formation within microchannels, and our own laboratory experience suggest that larger microchannels and increased device transparency are necessary to promote and support regeneration(Lacour, Atta et al 2008, Wieringa, Wiertz et al 2010, Srinivasan, Guo et al 2011, FitzGerald, Lago et al 2012, Srinivasan, Tahilramani et al in press). …”

“…Microchannel caliber is an important consideration to promote axon regeneration, device selectivity, and amplification of microchannel potentials. Very small microchannels, as small as 5 μm, have been demonstrated in vitro to optimally amplify axon potentials(Wieringa, Wiertz et al 2010). However, there is a balance between small caliber microchannels to amplify signals and improve selectivity and larger caliber microchannels, which promote and support regeneration.…”

“…In order to facilitate highly selective recordings, recent regenerative designs have incorporated microchannels through which axons regenerate and directly contact embedded electrodes (FitzGerald, Lacour et al 2009, Wieringa, Wiertz et al 2010, FitzGerald, Lago et al 2012, Srinivasan, Tahilramani et al in press). A principle challenge in peripheral neural interfacing is the detection of small amplitude peripheral neural signals amid much larger muscle signals.…”

“…The amplification of microchannel potentials improves in vitro within smaller microchannels where limiting extracellular volume further increases extracellular resistance. Smaller microchannels may also improve recording and stimulating selectivity by mechanically separating regenerating axons(Wieringa, Wiertz et al 2010). However, leveraging the amplifying properties of microchannels must also be balanced with design characteristics to optimize axon ingrowth and regeneration into microchannels.…”

Multi-Beam Interference Advances and Applications: Nano-Electronics, Photonic Crystals, Metamaterials, Subwavelength Structures, Optical Trapping, and Biomedical Structures

“…Some representative example applications are described here to enable gauging the impact that they have in biomedicine. In regenerating nerves, arrays of microchannels are needed to guide nerve growth [274]. In facilitating bone regrowth, periodic meshes are needed to retain and sequester bone morphogenetic protein.…”