There is currently no effective treatment strategy following traumatic injury to the peripheral nervous system (PNS) in either partial or full loss of extremity function. Recent work has demonstrated neural recording and electrical stimulation devices that allow for neural-motor control of prosthetic limbs. However, much improvement is required to reach the resolution of neural interfacing needed for physiological functionality. In addition to neural interfacing, tissue engineering strategies are potential means to restore functionality after traumatic injury to the PNS. However, current interventions are years from being effective in the clinic. Therefore, our goal is to engineer material platforms that both promote nerve regeneration and provide an electrical interface for prosthetic integration that is clinically relevant now.
To date, the influence of nerve channel geometry and dimensions of sub-200 μm scale on neural regeneration has been poorly investigated due to material processing. For interfacing with either the motor or sensory axons of the PNS, geometric constraints may provide a means for selectively regenerating axons to intimately interface electrodes with sensory or motor nerve fibers, respectively. Furthermore, topography robustly influences the orientation and length of neural growth. However, no technique currently exists to fabricate μm topography features on the interior surface of nerve guidance channels without the inclusion of films or rolling.
Herein, we present a new method for engineering polymeric nerve guidance channels with intrinsic topography or recording electrodes. Utilizing a thermal drawing process (TDP), macro-scale preforms of biocompatible polyetherimide were made with rectangular and cylindrical channels. Topographical features or electrodes composed of conductive polyethylene were machined and added to the preforms. TDP reduced the cross-sectional dimensions by up to 200 times while maintaining the original geometries. Rectangular, rectangular with microgrooves, and cyclindrical neural growth channels with dimensions 30-200 μm were evaluated in vitro for their influence on neurite outgrowth from primary dorsal root ganglia (DRGs). Total distance of neurite outgrowth into the channel as well as the orientation of neurite extension and cell nuclei within the channel were measured with respect to the geometry and dimensions of the growth channel. Preliminary data suggests that narrower channels (40-60 μm) enhance the orientation of DRG outgrowth compared to larger channels (>100 μm), but very limited growth is observed in small channels (<40 μm). However, inclusion of microgrooves within the large channel increases neurite orientation. These results demonstrate our ability to utilize the TDP to design new polymeric nerve guidance channels as a strategy for PNS regeneration and neural interfacing.
Massachusetts Institute of Technology, Massachusetts Institute of Technology
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