Photoacoustic Silk Scaffolds for Neural stimulation and Regeneration

Neural interfaces using biocompatible scaffolds provide crucial properties for the functional repair of nerve injuries and neurodegenerative diseases, including cell adhesion, structural support, and mass transport. Neural stimulation has also been found to be effective in promoting neural regeneration. This work provides a new strategy to integrate photoacoustic (PA) neural stimulation into hydrogel scaffolds using a nanocomposite hydrogel approach. Specifically, polyethylene glycol (PEG)-functionalized carbon nanotubes (CNT), highly efficient photoacoustic agents, are embedded into silk fibroin to form biocompatible and soft photoacoustic materials. We show that these photoacoustic functional scaffolds enable non-genetic activation of neurons with a spatial precision defined by the area of light illumination, promoting neuron regeneration. These CNT/silk scaffolds offered reliable and repeatable photoacoustic neural stimulation. 94% of photoacoustic stimulated neurons exhibit a fluorescence change larger than 10% in calcium imaging in the light illuminated area. The on-demand photoacoustic stimulation increased neurite outgrowth by 1.74-fold in a dorsal root ganglion model, when compared to the unstimulated group. We also confirmed that photoacoustic neural stimulation promoted neurite outgrowth by impacting the brain-derived neurotrophic factor (BDNF) pathway. As a multifunctional neural scaffold, CNT/silk scaffolds demonstrated non-genetic PA neural stimulation functions and promoted neurite outgrowth, providing a new method for non-pharmacological neural regeneration.