3D Printing of Cytocompatible Gelatin‐Cellulose‐Alginate Blend Hydrogels

Abstract

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...

TEMPO-Oxidized Cellulose Nanofiber-Alginate Hydrogel as a Bioink for Human Meniscus Tissue Engineering

“…Beyond rheological properties, the bioink needs to be crosslinkable to retain 3D structures and provide appropriate mechanical properties to the bioprinted constructs (Markstedt et al, 2015;Paxton et al, 2017). Alginate has been proven as a promising crosslinkable material for 3D bioprinting (Markstedt et al, 2015;Müller et al, 2017;Nguyen et al, 2017;Gatenholm et al, 2018;Göhl et al, 2018;Hiller et al, 2018;Wu et al, 2018;Yang et al, 2018;Heggset et al, 2019;Jessop et al, 2019;Ojansivu et al, 2019;Erkoc et al, 2020;Schwarz et al, 2020). It can form a stable hydrogel in the presence of divalent cations such as Ca 2+ and Ba 2+ due to the ionic interaction between the cation and the carboxyl functional group by forming "egg-box"calcium linked junctions (Li et al, 2007a).…”

“…It can form a stable hydrogel in the presence of divalent cations such as Ca 2+ and Ba 2+ due to the ionic interaction between the cation and the carboxyl functional group by forming "egg-box"calcium linked junctions (Li et al, 2007a). Alginate is usually mixed with other biomaterials to achieve higher printing resolution (Markstedt et al, 2015;Müller et al, 2017;Nguyen et al, 2017;Heggset et al, 2019;Jessop et al, 2019;Erkoc et al, 2020).…”

3D Printing of Alginate-Natural Clay Hydrogel-Based Nanocomposites

“…In recent years, alginate-based hydrogels were frequently used in the 3D(bio)printing process of specially designed scaffolds [ 3 , 4 , 5 , 6 , 7 ]. Through 3D printing, or the additive manufacturing technique, it is possible to fabricate accurate and reproducible, three-dimensional, alginate-based architectures by facile and material-saving layer-by-layer deposition, otherwise unattainable using conventional manufacturing techniques.…”

“…The 3D-printed alginate constructs present a low form fidelity and are unstable in physical conditions. Moreover, increasing the concentration of alginate has no beneficial effect on cell viability and proliferative capacity [ 2 , 3 , 4 ].…”

Current Advances in 3D Bioprinting Technology and Its Applications for Tissue Engineering

“…Singh et al mixed collagen type B and silk for the optimization and development of a crosslinker-free and printable bio-ink in cartilage engineering [58]. Erkoc et al blended gelatin type A, cellulose, and alginate to conduct swelling and degradation tests using crosslinkers of glutaraldehyde or CaCl 2 [59]. Based on these previous studies, the selection of gelatin type was dependent on the purpose of use.…”