Crafting Nanostructured Neural Interfaces with Hydrogel Particles

Central nervous system neural device functionality hinges on effective communication with surrounding neurons. This depends on both the permissiveness of the device material to promote neuron integration and the ability of the device to avoid a chronic inflammatory response. Here, a facile approach has been developed exploring the multiple functionalities of hydrogel particles to provide cues to impart neural integration for such materials. Three distinct, yet interconnected tasks were undertaken: investigating hydrogel particle-modified substrate neuron integration and central nervous system inflammatory response, investigating guided hydrogel particle adsorption, and investigating hydrogel particles as local reservoirs for counteracting adverse effects from oxidative species.

The potential of hydrogel particle modification on planar substrates and subsequent cell response to such substrates was investigated. The particle adsorption process can be tuned to control particle surface density by varying the adsorption time and the concentration of the original colloidal suspension. Using the PC12 cell line and primary cortical neurons derived from chick embryo, the particle-adsorbed surface readily supported robust cell adhesion and differentiation. For central nervous system inflammatory cell types NIH 3T3, RAW 264.7, and A172, the hydrogel particle-modified substrates elicited cell adhesion, sustained cell metabolic activity, while RAW 264.7 and A172 cells did not morphologically appear activated.

Hydrogel particles were investigated as directional cues for neuron adhesion and growth. PC12 cells preferentially adhered to HP-patterned regions of LbL-primed substrates. PC12 cell neurite outgrowth did not preferentially extend along the edge of stripe patterns, which may be due to selected pattern width and spacing.

Potential of hydrogel particles to provide local therapeutic utility to combat oxidative stress was investigated with the neuroprotective antioxidant resveratrol. Results demonstrated that resveratrol could be loaded into free and surface-adsorbed hydrogel particles. The loaded resveratrol remained bioactive overtime and could provide antioxidant activity to PC12 cells following an oxidative stress trigger.

Collectively, these results help lay the groundwork to design the hydrogel particle system for future in vitro and in vivo investigations to ultimately realize stable long-term neural device communication.