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Photopolymerized micropatterns with high feature frequencies overcome chemorepulsive borders to direct neurite growth
Journal article   Open access   Peer reviewed

Photopolymerized micropatterns with high feature frequencies overcome chemorepulsive borders to direct neurite growth

Bradley W Tuft, Linjing Xu, Braden Leigh, Daniel Lee, C. Allan Guymon and Marlan R Hansen
Journal of tissue engineering and regenerative medicine, Vol.12(3), pp.e1392-e1403
03/2018
DOI: 10.1002/term.2527
PMCID: PMC5787405
PMID: 28753740
url
https://doi.org/10.1002/term.2527View
Published (Version of record) Open Access

Abstract

Developing and regenerating neurites respond to a variety of biophysical and biochemical cues in their micro‐environment to reach target cells and establish appropriate synapses. Defining the hierarchal relationship of both types of cues to direct neurite growth carries broad significance for neural development, regeneration, and, in particular, engineering of neural prostheses that improve tissue integration with native neural networks. In this work, chemorepulsive biochemical borders are established on substrates with a range of surface microfeatures to determine the potential of physical cues to overcome conflicting biochemical cues. Physical micropatterns are fabricated using photomasking techniques to spatially control photoinitiation events of the polymerization. Temporal control of the reaction allows for generation of microfeatures with the same amplitude across a range of feature frequencies or periodicities. The micropatterned substrates are then modified with repulsive chemical borders between laminin and either EphA4‐Fc or tenascin C that compete with the surface microfeatures to direct neurite growth. Behaviour of neurites from spiral ganglion and trigeminal neurons is characterized at biochemical borders as cross, turn, stop, or repel events. Both the chemical borders and physical patterns significantly influence neurite pathfinding. On unpatterned surfaces, most neurites that originate on laminin are deterred by the border with tenascin C or EphA4‐Fc. Importantly, substrates with frequent micropattern features overcome the influence of the chemorepulsive border to dominate neurite trajectory. Designing prosthesis interfaces with appropriate surface features may allow for spatially organized neurite outgrowth in vivo even in the presence of conflicting biochemical cues in native target tissues.
photopolymerization methacrylate neural regeneration neural prosthesis cochlear implant

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