Photoacoustic Carbon Nanotubes Embedded Silk Scaffolds for Neural Stimulation and Regeneration

Abstract

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 2 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 1.74fold 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.

Electrospun Carbon Nanotube-Based Scaffolds Exhibit High Conductivity and Cytocompatibility for Tissue Engineering Applications

“…These photoacoustic properties have been shown to enable light-triggered depolarization of neurons without the need for genetic manipulation (such as the case in optogenetics), as well as to enhance neurite outgrowth. 46 …”

High-precision neural stimulation through optoacoustic emitters

“…According to Eq. (10), materials with superior light absorption coefficient (e.g., graphite , 36 , 44 , 51 carbon nanotubes (CNT) , 37 , 38 , 52 gold nanoparticles , 53 , 54 and polymer nanoparticles 39 ) and large thermal expansion coefficient [e.g., polydimethylsiloxane (PDMS) , 37 epoxy 36 , 44 ] could be utilized to boost the absorption and expansion, respectively, subsequently producing acoustic waves with a high pressure. 45 …”

“…Zheng et al. recently described a silk-based optoacoustic film with CNTs using a hydrogel nanocomposite approach 38 [ Fig. 4(a) ].…”

“…(a) Principle of optoacoustic generation based on varied absorption agents. Inset: Example absorption agents including graphite, 36 CNT, 37 , 38 and PANs. 39 (b) Optoacoustic stimulation platforms based on optical fibers, biocompatible films, and nanotransducers.…”

“… 37 Toward scalable and potentially noninvasive stimulation, a film-based optoacoustic silk scaffold for neural stimulation and regeneration has been developed by Zheng et al. 38 [ Fig. 1(b) , middle].…”