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International Journal of Bioprinting                                           3D bone: Current & future




                 hydrogels are often used in DIW, inkjet, LAP, and   different chemically modified forms in hydrogels.
                 DLP bioprinting technologies. 65                   In  this  regard, modified  cellulose  hydrogels  have
                                                                    good mechanical properties, and cellulose is an
            (viii)  dECM: dECM provides the most native-like                       70
                 microenvironment for cells as a hydrogel material. It   affordable material.
                 contains all the components of the ECM and growth   (x)   PEG and its derivatives: PEG is a synthetic
                 factors commonly found in native tissues; therefore,   biocompatible  polymer  that  is  highly  hydrophilic
                 it can promote cell proliferation and differentiation.    and has a high water-absorbing capacity.
                                                          7
                 The production of dECM is tissue-specific, but the   Additionally, its aqueous solution has a low viscosity.
                 tissue is generally exposed to physical, chemical,   In 3D bioprinting, PEGDA and PEG methacrylate
                 or enzymatic stressors to remove the cellular      (PEGDMA)  are  often used as  they are highly
                 components. These methods can oftentimes be        photocurable. PEGDA features rapid and stable
                 complicated and expensive. In addition, dECM-      crosslinking, good mechanical properties, good
                 based hydrogels are challenging to use for 3D      shape retention, high resolution, and high resistance
                 bioprinting, as they have low viscosity and poor   to swelling in the aqueous environment. However,
                 mechanical properties, making it difficult to regulate   PEGDA and PEGMA have low degradation rates and
                 their temperature-dependent crosslinking and rapid   poor cell adhesion, and they are often combined with
                 degradation. As such, dECM is usually mixed with   other organic hydrogel components (e.g., GelMA) or
                 other hydrogel materials for use in DIW, LAB, and   inorganic components (e.g., HA) to improve their
                 electrospun bioprinters. 66-69                     properties. PEG-based hydrogels are commonly
                                                                    used in DIW, inkjet, and DLP bioprinters. 39,71
            (ix)  Cellulose: Cellulose is a biocompatible and bioactive
                 natural hydrophilic polymer. Due to the abundance   4.2.3 Additional inorganic components
                 of hydroxyl groups and its poor biodegradability,   Bone tissue is a complex mineralized tissue with a rigid
                 cellulose  is  used  not  in  its  natural  form  but  in   ECM that is mainly composed of HA. Additionally, the two


            Table 5. Materials used in bone 3D bioprinting

             Type of   Material     Benefits            Drawbacks               Crosslinking    3D printing
             material                                                           mechanism       technique
             Hard scaffold  Polycaprolactone  Good biocompatibility;   Slow degradation; poor cell   N/A  Extrusion
                       (PCL) 89,90  biodegradable; easy to print  adhesion
                       PEGDA 89,91-94  Biocompatible; fast   Poor mechanical properties  Photo-crosslinking  Extrusion; SLA;
                                    degradation; easy to print                                  DLP
                       Polylactic acid   Biodegradable;   Slow degradation; poor cell   N/A     Extrusion
                       (PLA)        biocompatible; easy to print;   adhesion
                                    good mechanical strength
             Hydrogel  Alginate     Low cost; good      Low bioactivity; poor cell   Ionic crosslinking  Extrusion; inkjet;
                                    biocompatibility;   adhesion; poor mechanical               laser-assisted
                                    biodegradable; low   properties; limited stability in the
                                    immunogenicity; shear-  presence of antioxidants.; poor
                                    thinning behavior   bone conductivity; poor 3D shape
                                                        maintenance
                       Gelatin      Biocompatible;      Fast degradation; poor mechanical  Thermal crosslinking  Extrusion; inkjet;
                                    biodegradable; reversible   properties; slow gelation       laser-assisted
                                    gelation; low cost
                       Gelatin      Biocompatible;      High cost; cell damage by   Photo-crosslinking  Extrusion; DLP;
                       methacryloyl   biodegradable; easy to   blue or UV light                 electrospun
                       (GelMA)      crosslink with photo-
                                    initiators; fast crosslinking;
                                    3D shape maintenance
                       Chitosan 63  Good biocompatibility; good   Fast degradation; poor mechanical  Ionic crosslinking;   Extrusion; DLP;
                                    cell adhesion; osteogenic   properties; high cost  photo-crosslinking;    laser-assisted
                                    potential                                   self-assembly
                                                                                                      (Continued)


            Volume 10 Issue 3 (2024)                       161                                doi: 10.36922/ijb.2056
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