MXene-chitosan photo-responsive conduit for wireless optogenetic stimulation to enhance neural regeneration and functional recovery after optic nerve injury.

Abstract

Optic nerve injury triggers progressive degeneration of retinal ganglion cells (RGCs) and axonal loss, driven by inhibitory microenvironmental factors such as glial scarring, myelin debris, and growth-inhibitory signaling. Physical stimuli such as photothermal and photoelectric stimulations have gained attention, yet little is known about their potential on normal cells or the optic nerve due to setbacks from over-exposure. Photothermal stimulus presents photoelectric cues and, at the same time, energy conversion for heat generation. Herein, a bio-functional platform was designed by incorporating W_1.33C i-MXene into a chitosan solution, further crosslinked with Genipin to give a porous, interconnected, and biodegradable conduit. The photoelectric platform allowed neural differentiation of PC12 cells through a substantial effect on the Calcium (Ca²⁺) ion channel. Further, we used the optic nerve crush (ONC) model to investigate the photo-stimulation effect of the conduit after ONC. Light stimulation of the WMC conduit promoted the protection of RGC and improved the visual function by modulating neural-related proteins and the downstream signaling cascade for nerve regeneration through the l-type voltage-gated calcium channel (L-VGCC). This multifunctional platform synergistically combines MXene's photoconductivity with chitosan's biocompatibility, establishing a scalable strategy for wireless neural stimulation and tissue engineering-mediated functional recovery after central nervous system injury. STATEMENT OF SIGNIFICANCE: The objective of this study was to design and fabricate a bio-functional, porous, and biodegradable platform by incorporating MXene into chitosan. This new conduit was expected to act as a photoelectric platform, allowing neural differentiation through a substantial effect on the calcium ion channel. W_1.33C i-MXene-chitosan (WMC) was the representative platform under a photothermal stimulus characterized by photoelectric cue and energy conversion to generate heat. In a rat optic nerve crush model, the conduit induced the protection of RGC and improved visual function by modulating neural-related proteins and the downstream signaling cascade for nerve regeneration through the l-type voltage-gated calcium channel (L-VGCC). This multifunctional platform synergistically combines MXenes' photoconductivity with chitosan's biocompatibility, establishing a scalable strategy for wireless neural stimulation.