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International Journal of Bioprinting                           3D-Printed GelMA biomaterials in cartilage repair




 Table 1. Modifications of GelMA hydrogels in cartilage tissue engineering
 Materials  Modifications  Aims  Properties of modification  Characteristics of GelMA after modifications  In vitro outcomes  In vivo outcomes
 GelMA  Increased concentration or ultraviolet   Improve mechanical properties  N/A  Controlled stiffness and swelling properties  N/A  N/A
 (UV) irradiation time
 GelMA  Introduction of oligomer of dopamine   Improve mechanical properties  Good biocompatibility; adhesive property;   Enhanced toughness and resilience; controlled   Promoted chondrocyte adhesion and   Good cartilage repair abilities
 methacrylate (ODMA)  tunable property; versatility  degradation rate; continued protein release  proliferation
 GelMA  Incorporation of polyacrylamide (PAM)  Improve mechanical properties  Biocompatibility; hydrophilicity; controlled   Enhanced compression strength and improved   Good cell adhesion and biocompatibility   Good cartilage repair ability in rabbit knee
 mechanical properties; versatility  elasticity; a favorable degradation rate and sustained  in vitro  cartilage defect model
             protein release
 GelMA  Incorporation of thiolated heparin   Improve integration and   Ability to bind to various biomolecules and   Preserved anticoagulation and growth for signaling   Greater cell differentiation and cartilage   N/A
 (HepSH)  adhesion  surfaces; biocompatibility; anticoagulant   capacity; promoted cell viability and chondrocyte   matrix deposition in vitro
 properties; versatility  phenotype.
 GelMA with ε-polylysine  Modified Gel-EPL/B hydrogel  Improve integration and   EPL: Interact with negatively charged cell   Improved mechanical properties and better suited   Induction of more ECM and improved   Promoted tissue repair of cartilage defects
 (EPL) and phenylboronic   adhesion  surfaces and ECM; biocompatibility and   for chondrocyte production  chondrogenesis
 acid (PBA)  antimicrobial properties;
 PBA: Binding properties to sugars;
 biocompatibility; stability; versatility
 GelMA  Microbial transglutaminase  Seamless integration  A significant increase in adhesive strength  N/A  N/A
 PEGDA/GelMA  PEGDA  Promote adhesion and improve  Biocompatibility; versatility; hydrophilicity;   Different adhesion ligand densities and stiffness   N/A  Improved integration and adhesion with in situ
 mechanical properties  photopolymerization; biodegradability  properties     tissues
 GelMA/AGA  Grafted glucosamine molecules onto   Provide an effective approach   Biocompatibility; anti-inflammatory;   More than 87.7% of 15% (w/v) GelMA hydrogel   Better biocompatibility, larger cell   Best integration in in vivo rabbit cartilage repair
 acrylate groups  of GlcN delivery to a target site    cartilage-building properties  was grafted with AGA  attachment, and higher cell viability
 GelMA  Introduction of tyrosine (Tyr) groups  Improve mechanical properties  Form strong hydrogen bonds  Tyramine binding to proteins in native cartilage   Neocartilage formation from embedded   Improved adhesion to the surrounding tissue,
             leads to a 15-fold increment in the adhesive   chondroprogenitor cells is demonstrated   and improved lateral integration of neocartilage
             strength of the bioglue compared to pristine GelMA  in vitro
 GelMA/ECM-PFS  Introduction of RGD peptides PFS   Improve integration and   No changes in physical properties  Enhanced mechanical properties; recruitment of   GelMA/ECM-PFS could regulate the   Facilitated recruitment and chondrogenesis of
 ( peptide sequence PFSSTKT)  adhesion  BMSCs; improved hyaline cartilage repair in rabbits  migration of rabbit BMSCs  BMSCs, and promoted hyaline cartilage repair
                                                                              in rabbit
 GelMA/PLLA  Poly(lactic acid) (PLLA)  Improve printing fidelity and   Biocompatibility; biodegradability;   Fabricated constructs with a compressive stress   Support BMSCs proliferation and   N/A
 mechanical strengths    mechanical strength; versatility; controlled   of ≈150 kPa even after 100 cyclical compression   chondrogenesis
 release     loading (up to 40% of strain)
 GelMA/PEGDA/CSMA  PEGDA/CSMA  Adjust mechanical strength   Possess suitable compressive elastic modulus and   Provide a 3D support for BMSCs; the   N/A
 and guide chondrogenesis of   degradation rate  differentiation lineage could be changed by
 BMSCs                                         adjusting the percentage of CSMA


            improvement over traditional fabrication techniques. This   manner, which makes them good carriers owing to the
            is achieved by incorporating various cells, growth factors,   controlled release of specific growth factors in cartilage
            and other tissue components and utilizing computer   defects. Growth factors have the potential to enhance
            technology to closely mimic the complex architectures of   current cartilage repair through various mechanisms, such
            the target tissues (Figure 7). Here, we provide a summary   as recruiting chondrocytes, stimulating their proliferation,
            of the results and characteristics of 3D-printed GelMA   and enhancing cartilage matrix formation [32,33] . Among
            scaffolds loaded with cells, growth factors, or other   various growth factors, transforming growth factor-β3
            materials for use in articular cartilage tissue engineering.   (TGF-β3) has been proven to be the most effective in
            This information will be valuable for future research and   inducing chondrogenesis of stem cells in many studies.
            development of GelMA and 3D printing techniques for   To this end, Wang et al.  constructed a GelMA scaffold
                                                                                  [34]
            cartilage repair. By harnessing the potential of 3D printing   functionalized with alginate sulfate, which has a high
            technology, it may be possible to develop more effective   affinity to TGF-β3. This scaffold enabled sustained
            and personalized treatments for articular cartilage defects,   release of TGF-β3, supporting robust chondrogenic
            ultimately for the application in clinical settings.  differentiation of mesenchymal stem cells (MSCs) in vitro
                                                               and in nude mice. Insulin-like growth factor-1 (IGF-
            5.1. Growth factors                                1) is a hormone that possesses anti-apoptotic and anti-
            One of the distinguishing characteristics of GelMA-  inflammatory properties, promotes the production of
            based hydrogels is their ability to degrade in a controlled   ECM by chondrocytes through paracrine mechanisms,

            Volume 9 Issue 6 (2023)                        247                         https://doi.org/10.36922/ijb.0116
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