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











































            Figure 3. (A) In situ modifications: adding modified materials to the culture medium and changing the conditions of the medium. (B) Ex situ modifica-
            tions: adding modified materials to the generated BC.
            (Young’s modulus up to 78 GPa), porous structure, and   microspheres  in  a  bacterial  medium  and  made  scaffolds
            excellent biocompatibility . Therefore, BNC has become   after BNC generation, and then removed the paraffin wax
                                 [41]
            a highly valued material for 3D printing in TE.    microspheres to obtain bone scaffolds with large porosity .
                                                                                                           [45]
                                                               Ex situ modifications refer to physical or chemical
               Different bacterial sources produce BNC with different                                 [44]
            properties. Among these,  Acetobacter  xylinum and   modifications after their formation (Figure  3B) . Fang
                                                               et al. used hydroxyapatite to modify the generated BNC to
            Gluconacetobacter xylinus are the most widespread sources.   stimulate osteoblast proliferation and differentiation .
                                                                                                        [46]
            A. xylinum can polymerize up to 200,000 glucose molecules
            per second via cellulose synthase . Polymerized glucose   2.3.2. BNC 3D bioprinting in cartilage and bone repair
                                       [42]
            chains are assembled from sub-elementary fibrils to   BNC is limited in 3D printing because of the complex
            microfibrils, and then further into tight ribbons. BNC are   protofibrous structure that causes it to frequently clog the
            more expensive than other cellulose derivatives because of   nozzles of 3D printers and discourage cell migration .
                                                                                                           [47]
            the high cost of the medium used to make BNC. However,   Therefore, obtaining BNC dispersions is important for the
            numerous techniques, including strain mutagenesis, have   preparation of BNC-based scaffolds. Given that TEMPO-
            been used to boost the production of synthetic cellulose   oxidized NFC easily forms nanofibrous monomers in
            from A. xylinum .                                  aqueous solutions, TEMPO-mediated oxidation is also
                         [43]
               To optimize BNC for TE, different methods have   widely used to decompose BNC and has been extensively
            been investigated to modify it, including  in situ and  ex   investigated for the preparation of bone TE scaffolds.
            situ modifications. In situ modification refers to changing   At present, maleic acid (MA) is considered an excellent
            the  environment  and conditions  of bacterial  culture   reagent for the preparation of nanocellulose monomers .
                                                                                                           [48]
            (Figure 3A) . Classical  in situ modifications are often   Wang et al. obtained a dispersed BNC-gel composite ink
                      [44]
            used to modulate the porosity of BNC scaffolds for bone   by untwisting the tight protofibrous BNC network using
            TE.  For  example,  Zaborowska  et  al.  placed  paraffin  wax   MA and obtained a bone TE scaffold containing primary


            Volume 9 Issue 1 (2023)olume 9 Issue 1 (2023)
            V                                              218                      https://doi.org/10.18063/ijb.v9i1.637
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