Mechanically optimized hydrogel enhances functional recovery after spinal cord injury

Spinal cord injury (SCI) is a highly debilitating condition. Following SCI, the number of M1 microglia in the spinal cord increases, secreting numerous inflammatory factors that exacerbate the inflammatory response and activate resting astrocytes to form the neurotoxic A1 astrocytes. Hydrogels have good biocompatibility and their mechanical properties and bioactivity can be optimized by adjusting the ratios of their composition, whereby spinal cord repair can be promoted. This study aimed to compare the characteristics and bioefficacy of two hydrogels with different proportions of methacryloylated gelatin (GelMA) and pluronic F127 diacrylate, namely G5F and G10F hydrogels, prepared with 0.05 and 0.1 g/mL GelMA, respectively. Both the G5F and G10F hydrogels exhibited favorable properties, including plasticity, mechanical stability, and shear-thinning behavior. However, compared with the G5F hydrogel, the G10F hydrogel demonstrated a larger compressive modulus, tensile modulus and toughness, as well as a greater pore size. C3 expression was lower in cultured astrocytes treated with the conditioned medium from microglia cultured within G10F than in lipopolysaccharide-treated astrocytes, indicating that the G10F hydrogel inhibited microglial activation. G10F transplantation promoted motor recovery post-SCI better than G5F transplantation, as indicated by higher Basso Mouse Scale scores, footprint analysis results, and reduced scar areas observed through hematoxylin-eosin and GFAP staining. Additionally, immunostaining for Iba1, Ki67, iNOS, NeuN, and cleaved Caspase-3 revealed that G10F suppressed inflammatory responses and neuronal death more effectively than G5F via multiple inflammatory signaling pathways. Therefore, optimizing the proportions of hydrogel components offers new prospects for SCI treatment.