Bifurcating microchannels as a scaffold to induce separation of regenerating neurites

Abstract

Many neural interfacing strategies, such as the sieve electrode and the cultured probe, rely on neurite growth to establish neural contact. But this growth is subject to natural fasciculation, compromising the effectiveness of these interfacing strategies by reducing potential selectivity. This in vitro study shows that the fasciculation mechanism can be manipulated by providing an appropriate microchannel scaffold to guide and influence growth, thereby achieving a high degree of selectivity. The microchannels employed have a bifurcation from a primary channel into two secondary channels. This bifurcating microstructure was able to support and promote fasciculated growth over 70% of the time for microchannels widths of 2.5, 5, 10 and 20 microm. Fasciculation is shown to be a strong force during ingrowth, with the initiation of neurite separation related to random spatial exploration. Narrower microchannels initiate separated growth better. Once separated growth starts fasciculation results in an even distribution of neurite growth across the bifurcation. The reduction from 20 microm to 10 microm wide channels also resulted in a 3-fold decrease in ingrowing neurites performing 180 degrees turns to exit the microchannel via the entrance. No neurite turning was observed for both the 5 and 2.5 microm wide channels.

Biomimetic Architectures for Peripheral Nerve Repair: A Review of Biofabrication Strategies

“…This includes the incorporation of topographical cues, based on in vitro studies that show neurite growth is directed by FA orientation in response to underlying aligned topographies . In addition, studies have also shown that microchannel structures can confine neurites and serve to effectively direct nerve growth . Furthermore, favorable cell–material interaction and cell adhesion are paramount to establishing sufficient neurite growth in the first place.…”

Recording Large Extracellular Spikes in Microchannels along Many Axonal Sites from Individual Neurons

“…Peyrin et al created ‘axon diodes,’ channels that narrow at one end, and orient the network in one direction [ 32 ]. Wieringa et al explored, how channel size influences axonal outgrowth and how bundles may be separated by cleverly designed bifurcations [ 33 ]. These systems were used in combination with microscopy.…”

Surface Microstructures on Planar Substrates and Textile Fibers Guide Neurite Outgrowth: A Scaffold Solution to Push Limits of Critical Nerve Defect Regeneration?

“…Diffusible [1] and surface bound molecule gradients [2], [3], [4], chemical surface patterning [5], [6] or mechanical structures like pillars [7], micromachined steps, ridges or groove gratings at the (sub-)micrometer scale are promising as guidance cues [8], [9], [10], [11], [12], [13], [14], [15].…”