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International Journal of Bioprinting                           3D bioprinting techniques & hydrogels materials




            composite alginate hydrogels for osteochondral repair in   functional groups, ligands, macromolecular side chains,
            future developments.                               etc. 139,140  Chitosan derivatives demonstrate excellent
                                                               biological  characteristics.  Additionally,  as  chitosan  is
            3.1.2. Methacryloyl-modified gelatin hydrogels     derived  from  shellfish  or  shrimp,  the  allergic  reaction
            Methacryloyl-modified gelatin (GelMA) is a gelatin   might also impact its clinical transformation. Waibel et al.
            derivative composed of methacryloyl side groups    evaluated its biosafety, and no adverse effects were found in
            (methacrylamide and methacrylate [MA]), with excellent   the subjects.  Further research is warranted to clarify this
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            cell adhesion properties due to its retention of most   issue in the future.
            functional amino acid motifs (e.g., RGD motifs). 131,132
            GelMA hydrogels have excellent biocompatibility, can   3.1.4. Hyaluronic acid hydrogels
            load cells, and maintain the controlled release of growth   Hyaluronic acid (HA) is an essential constituent of the
            factors, as well as the advantage of low immunogenicity,   ECM, and its molecular chain is alternately composed of
            making them widely used.  Jiang et al. fabricated a   repeating disaccharide units of β-1,4-D-glucuronate-β-
                                   133
            3D-printed platelet-rich plasma (PRP)-GelMA hydrogel   1,3-n-acetyl-d-glucosamine. 142,143  Owing to the diversity
            scaffold using DMD for osteochondral repair in a   of the repeating disaccharide unit, the HA molecule does
            rabbit model and compared the therapeutic effects of   not induce an immune response. In addition, HA can
            different concentrations of PRP on osteochondral repair.   cause macrophages to polarize from M1 type to M2 type
            They found that 20% of PRP exhibited the strongest   by targeting CD44  in vivo, exerting anti-inflammatory
            repair effect and could promote the polarization of   effects.  HA also has inherent properties against certain
                                                                    144
            M2 macrophages. 40                                 strains and antimicrobial delivery. Coupled with its
                                                               outstanding water retention capacity, biodegradability, and
               However, Enhancing the  mechanical  strength  of 3D   designability, it is extensively utilized in the fields of drug
            printed GelMA for soft tissue engineering applications.   delivery, cell culture, and regenerative medicine. 145,146
            Current methods to enhance their mechanical properties
            are mainly through crosslinking with other substances,   Nevertheless, its high vulnerability to enzymes
            such as nanomaterials and polymers.  Dong et al.   and weak mechanical properties impede its broader
                                             134
            prepared a GelMA-GelMA (G-G) homogeneous double-   application. 147  Fortunately,  there  are  numerous
            network hydrogel based on DLP 3D printing to improve its   multifunctional reactive  groups in  HA, and diverse
            mechanical strength. In addition, hydrogen bonding and   HA derivatives can be obtained by employing various
            crosslinking between HA and GelMA hydrogel can also play   chemical modification and crosslinking strategies to
                                                                                                            148
            a role in enhancing mechanical properties  (Figure 2i).  enhance their mechanical strength and stability
                                             135
                                                               (Figure 2i). For instance, HA can be chemically modified
            3.1.3. Chitosan hydrogels                          with photo-crosslinkable functional groups, such as MA,
            Chitosan is derived from chitin, which is abundant   to facilitate photo-crosslinking between HA molecules.
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            in nature and has satisfactory biocompatibility and   A HAMA hydrogel possesses enhanced mechanical
            biodegradability. It is an attractive candidate material   strength, making it suitable for constructing a variety
                               136
            for tissue engineering.  Chitosan hydrogels prepared   of hydrogels, such as microparticles, microneedles, and
            by  enzyme  crosslinking  can  support  the  proliferation   3D-printed scaffolds.  The biological properties of HA
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            of  chondrocytes  and  mesenchymal  stem   cells   can also be improved via oxidation or the introduction of
            (MSCs),  maintain  the  phenotype  and  morphology of   sulfhydryl and catechol, etc. 151-153
            chondrocytes, and promote the deposition of cartilage
                       137
            ECM  in vitro.   Sheehy et  al.  verified their capacity  to   3.2. Hydrogel composition
            support chondrogenesis and hypertrophy of MSCs. The   3.2.1. Hydrogel mixed with bioceramics
            chondroblast phenotype of MSCs was well retained after 8   Bioceramic materials, exemplified by calcium carbonate,
            weeks of chondrogenesis in vitro. In vivo, it was discovered   calcium phosphate, calcium sulfate, and their derivatives,
            that it promoted neither vascularization nor endochondral   possess  excellent  mechanical  properties,  which  can
            ossification, suggesting that it is a suitable material for   compensate for the weak mechanical properties of
            articular cartilage engineering. 138               hydrogels.  Furthermore, the inherent bone inducibility
                                                                       154
               However, chitosan possesses poor water solubility   and conductivity of bioceramics facilitate the proliferation
            under  physiological  conditions  and low  cell  adhesion,   and differentiation of MSCs in both scaffold-loaded and
            which constitutes the primary reason restricting its   bone defect sites, enhancing the repair capacity when
            application. Currently, the solubility and cell adhesion   combined with hydrogels to form bioinks. 155,156  The
            of chitosan derivatives are regulated by introducing   common applications of 3D bioprinting of hydrogel in

            Volume 10 Issue 6 (2024)                        74                                doi: 10.36922/ijb.4472
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