The advancements in 3D printing systems together with medical imaging devices, including magnetic resonance imaging (MRI) and computed tomography (CT), have made it possible to fabricate customized implantable scaffolds from computer-aided designs (CAD), which can precisely fit to the affected region in body of patients. [1,2] Hydrogels are widely preferred scaffold materials for 3D printing since they can mimic the natural tissues due to their high water content, porosity, and flexibility. [1,3] Additionally, they can be easily functionalized with biochemical and biophysical cues, and have easy fabrication processes. [4,5] Deriving therapeutic benefits such as supporting cell adhesion, promoting cell proliferation, and providing mechanical support for the tissue remodeling are desired for hydrogels. Physical, chemical, or biochemical crosslinking of homopolymer or copolymer solutions is typically used to form the hydrogels. [6] Along with synthetic polymers, the natural polymeric hydrogels can provide a stable environment for cells to grow, migrate, proliferate, and/or differentiate. [1] Natural polymers can be extracted from natural products via physical or chemical techniques in order to form hydrogels. The natural polymeric hydrogels, such as gelatin, [7,8] alginate, [9] fibrinogen, [10] hyaluronic acid, [11] cellulose, [12] and chitosan, [13] can dissolve in biofriendly inorganic solvents including phosphate-buffered saline (PBS) and cell culture medium. [6] Besides the well-known biocompatibility and biodegradability of natural polymeric hydrogels, their mechanical characteristics, however, limit potential applications as bioinks for manufacturing of scaffolds through 3D printing process. [14] Collagen-based biomaterials, used in most of the previous studies due to their intrinsic cell-adhesion sites, have been reported to have poor printability and long crosslinking durations. [15] Likewise, sodium alginate, which is a block copolymer of consecutive and alternately arranged β-d-mannuronic acid and α-l-guluronic acid residues, is a broadly preferred material since it is easily crosslinked via ionotropic gelation with divalent cations (e.g., Ca 2+ , Zn 2+). [16] However, alginate hydrogels require additional bioactivation step to trigger cell adhesion. [17] Another 3D bioprinting of hydrogels has gained great attention due to its potential to manufacture intricate and customized scaffolds that provide favored conditions for cell proliferation. Nevertheless, plain natural hydrogels can be easily disintegrated, and their mechanical strengths are usually insufficient for printing process. Hence, composite hydrogels are developed for 3D printing. This study aims to develop a hydrogel ink for extrusion-based 3D printing which is entirely composed of natural polymers, gelatin, alginate, and cellulose. Physicochemical interactions between the components of the intertwined gelatin-cellulose-alginate network are studied via altering copolymer ratios. The structure of the materials and porosity are assessed using infr...
