The field of tissue engineering favors the development of biomaterials that can support cell growth and regeneration, while being biocompatible, mechanically functional, biodegradable. Hydrogel biomaterials have lots of biomedical applications, including wound healing, cartilage repair, organ regeneration. We aim to develop functional hydrogels, which mimic tissue extracellular matrix by combining cellulose nanofibers (CNF) and chitosan (CHI) hydrogel in extrusion 3D printing. The flow behavior of CNF-filled CHI suspensions was investigated by rheology and the mechanical properties of the printed CHI/CNF hydrogels were studied by tensile testing. Fibroblast cells viability was assessed by LIVE/DEAD assays. The biodegradation of the cellulose nanoreinforcement in the hydrogels was enzymatically performed and investigated along the cell culture studies, to produce fully biodegradable tissue bioconstructs of tuned microstructure and mechanical properties. CNFs improved the extrudability of CHI-based inks, resolution, stability of printed constructs. The Newtonian viscosity of CHI-based inks increased at adding the CNFs. The nanofibers improved gelation and mechanical properties of printed hydrogels, in systems of low CHI and CNF concentrations. Young’s modulus and strength as high as 3.0 MPa and 1.5 MPa, respectively, were achieved for hydrogels of c(CHI) of 2% and CNF content of 0.4%. 3D cell growth was observed within the constructs. Enzyme-laden CHI/CNF scaffolds were printed, allowing controlled biodegradation of the hydrogels. These results are promising for the engineering of natural smart biomaterials, which are mechanically-performant, biocompatible, presenting controlled degradability for 3D cell growth.