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International Journal of Bioprinting                                         Hydrogels for 3D bioprinting



            properties. In addition, chitosan is also polycationic, and   adjusted the rheology of the hydrogel by changing the ratio
            its positive charge can generate electrostatic interactions   of Sil-MA to adapt to DLP-based printing. Among them,
            with negatively charged ECM molecules. Chitosan    30% of Sil-MA has suitable printability and good shape
            interacts  with  the  negatively  charged  cell  membrane  of   recovery. They fabricated a cricoid trachea by DLP-based
            microorganisms, causing the death of bacteria. Therefore,   printing for  in vitro testing. Sil-MA hydrogel provides
            this antibacterial property has expanded its application in   a suitable environment for the growth of chondrocytes
            the medical field [89,90] .                        and the formation of cartilage in vitro. The scaffold exists
                                                               in vitro for up to 4 weeks and degrades up to 50%.
               After the chitosan is modified, its performance
            will be greatly improved. After being methacrylated,
            chitosan can be used as a light-curable material for   4. Nanocomposite hydrogel bioink
            printing and crosslinking. Chang et al.  synthesized a   Despite the continuous investigations on natural and
                                            [91]
            water-soluble methacrylated glycol chitosan (MeGC)   synthetic hydrogels in recent decades, it is still challenging
            and produced an MeGC-based bioink loaded with MG-  to prepare tissue engineering scaffolds using single or
            63 cells using a visible light curing system with 12 μM   mixed hydrogel materials, and  some of the problems
            riboflavin as a photoinitiator. They made the MeGC   include  weak mechanical  properties, low  cell activity,
            solution by adjusting the pH of the solution in the first   and poor processability. These difficulties have prompted
            step; in the second step, MG-63 cells were suspended   researchers to find some suitable nanomaterials combined
            in a 3% MeGC solution containing 12 μM riboflavin   with hydrogels to improve the properties of hydrogels.
            and cured at 430–485 nm visible light for 30 to 90 s   Nanocomposite hydrogels have a wide range of applications
            using a visible light irradiator, and finally the hydrogel   in the fields of tissue engineering and regenerative
            containing the cells would be 3D-bioprinted. The results   medicine . Hassan  et al. summarized the methods and
                                                                      [93]
                                                                               [12]
            showed that the survival and value-added of MeGC-70   applications of nanomaterials in compounding hydrogel
            were high, and the rheological properties of the bioink   biopolymers. They found that the main natural biopolymers
            aqueous solution were optimized. CH materials can not   are SA and collagen derivatives. This part reviews the
            only be printed in the form of liquid bioink, but can also   commonly used nanomaterial composite hydrogels, such
            be extruded in the form of solid bioink. Zhang et al.    as inorganic nanomaterials, carbon-based nanomaterials,
                                                        [88]
            used hydrogel particles as the bioink for extrusion-  and nanofiber-based materials. A few researchers
            based 3D bioprinting. The particles are composed of   also use gold nanomaterials mixed with hydrogels as
            chitosan methacrylate (CHMA) and freeze-thawed     printed bioinks [94,95] .
            polyvinyl  alcohol  (PVA).  Under  the  action  of  chemical
            crosslinking and physical crosslinking, the hydrogel   4.1. Inorganic nanocomposite hydrogel
            was manufactured with fast self-healing and adjustable   Bioactive glass (BG), hydroxyapatite (HA), and Laponite
            mechanical properties (Figure  2A). The CHMA/PVA   are common inorganic nanomaterials with osteoinductive
            composite hydrogels are broken into particles during   properties. Therefore, inorganic nanomaterials are usually
            extrusion and then a printable hydrogel is formed through   mixed with hydrogels to repair bone and cartilage.
            the hydrogen bonding between chitosan and PVA chains.   According to related reports, the bioactive ions released
            The  innovative  self-healing  hydrogel  particles  exhibit   by the BG during degradation can promote cell adhesion,
            excellent shear thinning, gel-sol transition, and good   proliferation, and differentiation, and accelerate tissue
            yield strength during extrusion printing. Besides, the self-  vascularization and increase expansion force. It is currently
            supporting scaffold can adequately induce the growth,   the only material that can be combined with bone tissues
            proliferation, and differentiation of bone marrow-derived   and connected with soft tissues . Tissue engineering
                                                                                          [96]
            MSCs. In addition to the above modification methods,   has developed rapidly in the field of regeneration of hard
            mixing  chitosan  with other  polymers,  such  as PEG,  to   tissues, such as bone and cartilage, but bone graft therapy
            prepare bioinks is also an effective way .         is very limited in clinical practice. Bones have strong self-
                                           [39]
                                                               regeneration ability, and self-recovery is more successful
            3.3.3. Modified silk fibroin                       for small-scale bone defects. However, for large-scale bone
            In addition to gelatin and chitosan, many researchers also   defects that cannot be cured on their own, external bone
            have modified silk fibroin to improve their mechanical   scaffolds are needed to help bone regeneration and healing.
            properties and to modulate their degradation rates. It is   Bone scaffolds need to meet some specific requirements
            usually modified with glycidyl methacrylate (GMA) as a   such as bone conduction, controllable pore size, mechanical
            photocrosslinked hydrogel for DLP-based printing [34,92] .   properties, and biocompatibility similar to natural bone,
            Kim  et al.  prepared SF-based bioink (Sil-MA) and   biodegradability, and adsorption capacity .
                                                                                                [97]
                     [92]
            Volume 9 Issue 5 (2023)                        218                         https://doi.org/10.18063/ijb.759
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