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



                                                               inks to increase their printability and then removed by
                 Ref.  [69]  [70]  [71]  [81]  [85]  [89]  [90]  [31]  adjusting the LCST.
                                                                  MC can be prepared in a variety of ways and is broadly
                 Biomedical applications  Bone and cartilage TE  Bone and cartilage TE  Bio-ink preparation  Cartilage TE  (a more regular distribution of methyl substituents along
                                                               classified  into  two  types:  homogeneous  distribution
                                                                                                           [64]
                                                               the  chains)  and  heterogeneous  distribution   (random
                                                                                                   [65]
                                                               distribution of the substituents). MC derivatives with DS
                                                               between 1.3 and 2.5 are water soluble, while those with DS
                                               Bone TE
                                           Bone TE
                                                          Bone TE
                         Bone TE
                                                               more than 2.5 are soluble in organic solvents .
                                                                                                  [59]
                                                               3.1.2. MC 3D bioprinting in cartilage and bone repair
                                                               MC is applied in bone TE in three main aspects: (i) as a
                                                               support ink, (ii) as a sacrificial ink, and (iii) to increase the
                                                               viscosity of the blended bio-ink.
                                                                  Given the low viscosity of Alg inks described earlier, MC
                     Increase of the ink viscosity  Increase of the ink viscosity  Increase of ink viscosity   Improvement in the mechanical properties   Enhanced gel kinetics  Increase of ink viscosity Maintenance of the scaffold’s macroporosity   Increase of the viscosity  Improvement in the mechanical properties   Enhanced gel kinetics  Enhanced gel kinetics  plays a similar role to nanocellulose for printing high-fidelity
             Table 3. A summary of recent studies on 3D printing of cellulose derivatives-based materials for bone and cartilage TE
                                                               scaffolds obtained by mixing with Alg . Ahlfeld  et  al.
                                                                                               [66]
                                                               proposed the use of a self-setting calcium phosphate cement
                                                               (CPC) and Alg-MC bio-ink by multichannel 3D plotting to
                                                               simulate a multilayered osteochondral tissue structure .
                                                                                                           [67]
                 Functions  Sacrificial ink  Porogen  Shear thinning  of the scaffold  Shear thinning  of the scaffold  CPC is commonly accepted as the best bone replacement
                                                               material because of its similarity to the mineral composition
                                                               of bone and its  in vivo conversion into calcium-deficient
                     •
                                                          •
                                           •
                                             •
                                  •
                                    •
                                        •
                           •
                                •
                                                   •
                              •
                                                       •
                                                 •
                         •
                                               •
                                                               nanocrystalline hydroxyapatite (HAp), which is absorbed
                 Bio-ink  Yes  Yes  Yes  Yes  No  No  Yes  Yes  by  osteoclasts  for  bone  reconstruction . To simulate the
                                                                                              [68]
                                                               three-layer configuration of the osteochondral region, the
                                                               uppermost layer consists of a human mesenchymal stem
                                                               cells (MSCs)-laden Alg-MC fraction resembling the articular
                                                               cartilage surface, the calcified cartilage region consists
                     Human chondrocytes (hCh)  Mesenchymal stromal cells / primary osteoprogenitor cells  Mesenchymal stromal cells   MC3T3 cells/ bone marrow mesenchymal stem cells  Primary stem cells from human   exfoliated deciduous teeth  Bone marrow mesenchymal   Pre-osteoblast cells (MC3T3-E1)  of a biphasic interwoven network of cell-laden Alg-MC
                                                               and CPC, and the lowermost layer, the subchondral bone,
                                                               consists of CPC. Between days 7 and 21, the cells remain
                                                               highly active as they start to migrate aggressively from the
                 Cell lines                    None  stem cell  Alg-MC to the CPC chain and exhibit an extended, elongated
                                                               morphology . Kilian et al. used human chondrocyte (hCh)-
                                                                         [67]
                                                               loaded Alg-MC ink together with CPC using 3D plotting to
                                                               construct the osteochondral replacement scaffold described
                     MC/Alg/calcium phosphate cement   MC/Alg/plasma/calcium phosphate   MC/Alg/non-viral vector-pDNA   CMC/glycol chitosan/ lactoferrin  CMC/gelatin/beta-tricalcium phos-  HPMC/calcium magnesium phos-  HPMC-MA (hydroxy propyl methyl  cellulose of methacrylation)/silk   HEC/CNCs/glycerophosphate/CS  type II) on the scaffold was found .  [62]
                                                               above (Figure 4A and  B) . A significant formation of
                                                                                    [69]
                                                               cartilage ECM (i.e., sulfated glycosaminoglycans, collagen
                                                                                         [69]
                                                                  Ahlfeld  et  al.  developed  an  MC-based  supportive
                                                               hydrogel ink for 3D plotting to create clinically relevant
                 Ink composition  cement (CPC)  complexes  phate (β-TCP)  They designed MC as a support ink to co-print a human
                                                               geometries, including critical overhangs and cavities .
                                                               scaphoid bone model with CPC (Figure 4C) and used MC
                                                       fibroin
                       (CPC)
                                                 phate
                                                               as a sacrificial ink to create the cavity . As plasma contains
                                                                                           [62]
                                                               a huge variety of angiogenic factors, in a recent study, CPC/
                                                               plasma-Alg-MC was used to print a pre-vascularized bone
                 Cellulose     derivatives type  MC  MC  MC  CMC  CMC  HPMC  HPMC  HEC  tissue scaffold. The plasma-Alg-MC formed the lumen wall
                                                               of the constructs, and CPC was used as an external scaffold
                                                               (Figure 4D and E). Cells were found to cover the surface of
                                                               the lumen after 35 days .
                                                                                 [70]
            V                                              220                      https://doi.org/10.18063/ijb.v9i1.637
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