A Thermo-Photo-Ionic Crosslinked Gellan Gum Hydrogel with Gradient Biomechanic Modulation as a Neuromaterial for Peripheral Nerve Injury

Gellan gum (GG) is a promising biomaterial due to its biocompatibility, tunable gelation, and modifiability. This study investigates the influence of triple crosslinking mechanisms-thermal gelation, UV-induced covalent crosslinking, and ionic crosslinking-on the mechanical and physicochemical properties of GG-based hydrogels, designed to function as a neuromaterial with hierarchical neuro-architecture as a potential nerve substitute for peripheral nerve injury. Initial thermal gelation forms a physical network via double-helix junctions. Methacrylation introduces vinyl groups enabling UV crosslinking, while post-treatment with Mg²⁺ ions strengthens the network through ionic bridging with carboxylate groups. Plasticizers-glycerol and triethyl citrate-were incorporated to modulate chain mobility, network hydration, swelling behavior, and mechanical flexibility. Seven-day erosion studies showed that glycerol-containing hydrogels eroded 50-60% faster than those with triethyl citrate and up to 70% more than hydrogels without plasticizers, indicating increased hydrophilicity and matrix loosening. In contrast, triethyl citrate reduced erosion, likely due to tighter polymer chain interactions and reduced network porosity. Mechanical testing of 1% <i>v</i>/<i>v</i> methacrylated GG hydrogels revealed that 1.5% <i>v</i>/<i>v</i> triethyl citrate combined with UV curing (30-45 min) produced tensile strengths of 8.76-10.84 MPa. These findings underscore the synergistic effect of sequential crosslinking and plasticizer choice in tuning hydrogel mechanical properties for neuro application. The resulting hydrogels offer potential as a neuromaterial in peripheral nerve injury where gradient mechanical properties with hydration-responsive behavior are required.