Formation of Fiber-Rich Curdlan Gels with High Toughness and Anti-neuroinflammatory Effects

Polysaccharide gels consisting of nanofibers offer considerable promise for biomaterials; however, except for bacterial cellulose, nanofiber gels formed by solely natural polysaccharides are still rare. Here, we present a self-assembled polysaccharide nanofiber gel based on Curdlan, exhibiting high elasticity, toughness, and antineuroinflammatory effects. A gelling method, termed phase separation+annealing (PSA), facilitated the formation of Curdlan hydrogels with a dense network of self-assembling nanofibers (∼20 nm in diameter), structurally analogous to natural β-glucan fibrils in fungi. These hydrogels exhibited exceptional mechanical performance with a tensile strength of up to 2.1 MPa and a fracture strain of 361%. Structural and formation analyses via X-ray diffraction, scanning electron microscopy, differential scanning calorimetry, and molecular dynamics simulations demonstrated that the PSA method enabled the hierarchical organization of Curdlan chains into highly ordered triple helices, forming interconnected nanofibers. Additionally, the Curdlan hydrogels with enhanced nanofiber networks (CD-E, where “CD” denotes Curdlan and “E” refers to the annealing-induced enhanced nanofiber structure) exerted antineuroinflammatory effects in a lipopolysaccharide-induced neuroinflammation model by attenuating nitric oxide production, downregulating pro-inflammatory cytokines, and inhibiting iNOS and COX2 expression, while promoting a neuroprotective microglial phenotype via increased CD206 and decreased CD86 expression. These findings shed light onto Curdlan gels and can expand their applications from food additives to biomaterials.