Near-infrared-responsive bioink for photothermal biofabrication and modulation of human 3D neural activity

Abstract

Neuromodulation has gained significant interest in understanding neural mechanisms and treating neural disorders, with inhibition of neural activity crucial for neural communication and treating brain disorders. Thermoplasmonic modulation using gold nanoparticles is particularly promising due to its high spatiotemporal resolution, non-reliance on genetic modification, minimal invasiveness, and deep tissue penetration via near-infrared light. However, existing in vitro models that leverage the thermoplasmonic properties to inhibit neural activity are mainly limited to two dimensions and poorly replicate the properties of in vivo brain tissue.This study introduces a novel approach involving spatially controlled photothermal fabrication to realize a photosensitive thermogel for a three-dimensional neural in vitro model. Using the plasmonic properties of gold nanorods, precise heat release triggers local crosslinking in a chitosan-based solution, forming a scaffold with high accuracy in the shape of the laser irradiation spot. Results confirmed the safety of photothermal fabrication for embedded neuronal cells. The photosensitive scaffold developed in this study closely mimics the mechanical properties of brain tissue and enables precise modulation of 3D neural network activity, representing the first demonstration of thermoplasmonic-mediated inhibition in a human 3D neural model.This proof-of-concept study in hydrogel photothermal biofabrication suggests that the developed photosensitive scaffold could be a valuable tool for neural network research, enhancing understanding of brain functions and dysfunctions.

Keywords

• Neuromodulation
• Photothermal effect
• Biofabrication
• Hydrogel
• 3D human neuronal network
• Chitosan