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International Journal of Bioprinting                         Cellulose-based bio-inks for bone and cartilage TE



























            Figure 6. Development of 3D bioscaffolds with macroporous and interconnect microporous morphology from bicomponent ink containing NFC and
            CMC via the combination of DIW 3D printing, freeze-drying and DHT techniques.

            after DHT. Therefore, this technique may inspire pore size   3.4. HEC
            adjustment and mechanical property improvement of   Owing to its excellent shear-thinning behavior and
            cellulose-based scaffolds.                         outstanding rheological properties , along with its
                                                                                            [93]
                                                               biocompatibility, HEC is often used as an additive in
            3.3 Hydroxypropyl methylcellulose                  bioengineered inks to meet the bioprinting requirements.
            Hydroxypropyl methylcellulose (HPMC) is also a     Li  et  al. added HEC to several bio-inks with different
            cellulose  ether  derivative;  however,  it  is  available  in   crosslinks to evaluate its effects on the fidelity, degradation,
            different  substitution types  with limits  on methoxy   and rheology of bio-inks . The results show that HEC
                                                                                   [94]
                                    [87]
            and hydroxypropoxy groups . These groups provide   can improve the fidelity of these bio-inks without affecting
            various characteristics, including flexibility, hydration,   their crosslinks. In addition, HEC improves the LCST of
            gelation temperature, and LCST behavior. Moreover, in   the gel, enabling 3D bioprinting at near body temperature.
            medical engineering, HPMC is mainly used as a material   HEC  increases  the swelling rate  to  ensure  a water-rich
            for encapsulating drugs  or as an ink tackifier in TE   environment in the scaffold for increased cell activity and
                               [88]
            scaffolds . Götz et al. prepared degradable bone implants   nutrient delivery. Therefore, HEC can be used to modify
                   [89]
            using extrusion-based 3D printing with HPMC and    bio-inks in several ways. Maturavongsadit et al. prepared
                                             [89]
            calcium magnesium phosphate polymers . The addition   cell-laden nanocellulose/CS-based bio-inks for 3D
            of HPMC increased the viscosity and shear-thinning   bioprinting . The authors added HEC as a gelling agent
                                                                        [31]
            behavior of the ink. Ni et al. integrated SF and HPMC for   to  the CS-NCC  bio-ink  to improve  its  gelation  kinetics.
            printing a bone marrow MSCs-laden DN hydrogel for   The glyoxal groups in HEC interact with the amine group
            cartilage tissue repair . The β-sheet structure between   of CS via covalent crosslinking through the Schiff’s base
                              [90]
            SF molecules is formed via low-power ultrasonication of   reaction . With the addition of HEC, the gelation time of
                                                                     [95]
            SF and acts as the rigid first network, whereas the HPMC-  this hydrogel was significantly reduced without affecting the
            methacrylate anhydride (MAn) crosslink acts as the   biocompatibility of the 3D-bioprinted bone tissue scaffold.
            soft second network. HPMC modified with MA forms a
            tight bond between SF and HPMC-MAn because of the   4. Conclusion and outlook
            exposure of more hydrogen bonds that interact with the
            β-sheet.  Simultaneously, the presence of HPMC has a   In this review, we focus on the applications of nanocellulose
                                         [91]
            synergistic effect on the gelation of SF . This DN hydrogel   and cellulose derivatives in 3D bioprinting for bone and
            combines the advantages of the two different hydrogels   cartilage TE. As it meets the basic requirements of bio-inks and
            and has good mechanical properties . Moreover, loaded   is easily modified, nanocellulose has been widely used in 3D
                                         [92]
            bone marrow MSCs have high activity and proliferative   printing. T-NFC modified by TEMPO oxidation has a good
            tendencies. At the same time, high expression of cartilage-  nucleation effect on hydroxyapatite and is suitable for bone
            related genes, such as high mobility group-box gene9 (Sox   TE, while the anionic carboxylic acid group in T-NFC can
            9) and collagen type II (Col II), was detected.    form ionic crosslinks with cations to enhance the mechanical


            Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023)
            V                                              223                      https://doi.org/10.18063/ijb.v9i1.637
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