Comparison of PANI- and PEDOT:PSS-Incorporated GelMA Hydrogels for Neuronal Differentiation of SH-SY5Y Cells

Conductive hydrogels are widely pursued for neural tissue engineering, but the conventional route of polymerizing conductive monomers in situ requires toxic monomers or organic solvents and is incompatible with cell encapsulation. Here, conductive hydrogels were prepared in a single step by dispersing pre-polymerized polyaniline (PANI) particles or poly(3,4-ethylenedioxythiophene):poly(styrene sulfonate) (PEDOT:PSS) nanoparticles into a gelatin methacryloyl (GelMA) precursor and photocrosslinking, giving a simpler, cell-friendly route from an injectable precursor; the two polymers were compared directly within a single platform. PEDOT:PSS was uniformly integrated, whereas PANI progressively aggregated, and these differences in dispersibility were reflected in the microstructure, mechanical properties, and swelling behavior of the hydrogels. Both polymers increased the electrical conductance of the hydrogels; the increase was statistically significant for PANI but small in magnitude, and the cellular outcomes diverged in the opposite direction. Over 7 days, the PEDOT:PSS 0.2% group supported SH-SY5Y metabolic activity comparable to GelMA, whereas PANI reduced it. After neuronal induction, neurite outgrowth appeared most extensive in the PEDOT:PSS 0.2% hydrogels, with co-detection of βIII-tubulin, MAP2, and synaptophysin. Cells could also be encapsulated within the precursor and photocrosslinked in situ, remaining viable in all groups, demonstrating that the one-step route is compatible with three-dimensional cell-laden constructs. Because the conductance differences were small and ran opposite to the biological outcome, these findings indicate that the performance of GelMA-based conductive hydrogels is associated with polymer dispersibility, surface chemistry, and mechanical properties rather than with bulk conductance, and point to dispersion stability rather than intrinsic conductivity as the primary design variable at cell-compatible loadings, with GelMA/PEDOT:PSS as a candidate platform for neural tissue engineering.