A Thixotropic, Cell-Infiltrative Nanocellulose Hydrogel That Promotes in Vivo Tissue Remodeling

Injectable gels have been used in minimally invasive surgery for tissue regeneration and treatment of inflammatory diseases. However, polymeric hydrogels often fail in cell infiltration, because of the presence of dense, cross-linked molecular networks and a lack of bioactivity, which causes delayed tissue remodeling. Here, we report a thixotropic, cell-infiltrative hydrogel of biofunctionalized nanocellulose that topologically enhances cell infiltration and biochemically upregulates cellular activity for the promotion of tissue remodeling. Biodegradable, sulfonated nanocellulose forms a nanofibrous hydrogel, mimicking cellular microenvironments through cross-linking between nano-cellulose and gelatin. Resulting nanocellulose hydrogels showed thixotropy, allowing for single syringe injection. Nanofiber-based hydrogels possess high molecular permeability, which is due to nanoporous structures. Sulfonate groups on nanocellulose increase protein adsorption and induce cellular extension in vitro. Highly sulfonated nanocellulose hydrogels enhanced cell infiltration and vascularization upon implantation into rats. Macrophage polarization to M2 was observed in nanocellulose hydrogels, which may be involved in tissue remodeling. Injectable, biofunctionalized nanocellulose gels have enormous potential as artificial biomatrices to heal inflammatory diseases through manipulation of the immune system and promotion of tissue remodeling.