Engineering Nanocellulose Scaffolds: Property Modification Strategies and Mechanotransduction‐Driven Tissue Outcomes

ABSTRACT Nanocellulose is being increasingly used in biomedical applications because of its biocompatibility, mechanical robustness, tunable surface chemistry, and adjustable rheology. This review evaluates recent strategies for engineering cellulose nanofibrils, nanocrystals, and bacterial nanocellulose into cell‐instructive scaffolds for skin, bone, cartilage, vascular, and cardiac regeneration. We emphasize how chemical and structural modifications, such as oxidation, functionalization, grafting, crosslinking, alignment, templating, and composite formation, reshape key physicochemical properties, including charge, hydrophilicity, topography, porosity, viscoelasticity, and conductivity. These features were examined in relation to protein adsorption and cell sensing mechanisms governing focal adhesion assembly, cytoskeletal organization, and mechanotransduction. Mechanistic evidence specific to nanocellulose is highlighted, while insights from broader biomaterials research are cautiously incorporated, where direct data remain limited. Across tissue contexts, the current findings indicate that scaffold architecture and surface chemistry can modulate cell adhesion, migration, and differentiation, although pathway‐level validation in nanocellulose systems is still sparse. This review identifies major knowledge gaps, including the need for systematic mechanotransduction studies, standardized reporting of material properties, and clearer structure–function relationships to advance reproducible and translational scaffold design.