(42c) Neural Pathfinding On Photopolymerized Micropatterns With Varied Mechanical Properties

Neural prosthetics are intended to replace or substantially augment motor and sensory functions of neural pathways that have been lost or damaged due to physical trauma, disease, or genetics. However, performance of successful neural prosthetics, such as the cochlear implant (CI), has not significantly improved in recent years due to poor spatial resolution at the nerve-implant interface. Directing nerve cell processes towards target electrodes may reduce the problematic current spread and improve stimulatory specificity. Consequently, our work utilizes the spatial and temporal control inherent to photopolymerization methodology to fabricate micropatterned methacrylate polymers that direct nerve cell growth based on substrate topographic and stiffness cues. Micropatterned substrates are formed in a rapid, single-step reaction by selectively blocking initiating light with glass-chrome photomasks which have repeating line-space features with a pitch of 10-100 µm in width. The resultant pattern is a continuous series of ridges and grooves at regular intervals that can be used for cellular contact guidance studies. Micro-feature depth is controlled and reproducibly generated from 220±40nm to 16±1.3µm by shuttering the light source at different time steps during the reaction and by modulating photo-initiator concentration. Alignment of neural elements increases significantly with increasing feature amplitude and constant periodicity, as well as with decreasing periodicity and constant amplitude. Spiral ganglion neuron (SGN) neurite alignment strongly correlates (r = 0.93) with maximum feature slope. Glial cells such as spiral ganglion Schwann cells (SGSCs) and astrocytes (ACs) as well as neurites from peripheral nervous system trigeminal root ganglion (TRG) and dorsal root ganglion (DRG) also strongly respond to micro-features across the spatially patterned substrate surface. In addition to feature height and spating, neurite alignment correlates to material mechanical properties. Specifically, substrate stiffness is modified by varying the cross-link density of the final material by either increasing the amount of cross-linker in the prepolymer formulation or by increasing the size of the spacer unit between cross-links. SGN neurites were observed to align more strongly as substrate rigidity increased. Interestingly, the neurites responded to material modulii that were orders of magnitude greater (GPa) than what is typically encountered in a neural environment (kPa). The ultimate goal of the research is to develop materials that predictably orient regenerative nerve cell growth and improve neural prosthetic stimulatory specificity and, thus, improve patient outcomes.