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




            fabricated by traditional techniques. Nevertheless, there   is unable to create scaffolds that effectively mimic the
            are studies on the role of 3D-printed chondrocyte-laden   architecture of full-thickness articular cartilage even after
            GelMA hydrogels in promoting cartilage regeneration in   other biomaterials were added to modify their mechanical
            other cartilage regions like auricle  and menisci .  properties. Articular cartilage is a load-bearing tissue that
                                       [68]
                                                   [69]
               Taken together, incorporating cells in GelMA hydrogels   requires high mechanical robustness. Most of the GelMA-
            produced by 3D printing for cartilage tissue engineering has   based biomaterials are hydrogels with, oftentimes, relatively
            demonstrated promising results. Different cell types have   weak mechanical strength, which limits their application
            different advantages in promoting cartilage regeneration.   in the fabrication of articular cartilage tissues. To broaden
            Nevertheless, the best source of cells for use in cartilage   their applications in regenerative medicine, GelMA
            tissue engineering remains to be explored in the future .   hydrogels must be modified to enable the fabrication of 3D
                                                        [70]
            By incorporating different cell types, researchers can   constructs that are more biomimetic to the structure and
            exploit the wide array of application of GelMA hydrogels   function of real tissues and organs.
            with the help of 3D printing technology.              Secondly, the degradation rate of GelMA-based
                                                               biomaterials is not really aligned with the articular
            5.3. Exosomes                                      cartilage regeneration rate, which is also a disadvantage of
            Exosomes, extracellular vesicles secreted  by cells,  have   using biomaterials in tissue engineering.
            emerged as promising candidates for enhancing cartilage
            regeneration due to their ability to mediate cell-to-cell   Finally, a limitation intrinsic to GelMA-based
            communication and transfer of bioactive molecules.   biomaterials is their swelling behavior. Although these
            Studies have demonstrated that exosomes derived from   materials can be precisely 3D-printed according to
            MSCs can promote cartilage regeneration by suppressing   computational models, the resultant structures are
            inflammation and inducing chondrogenesis. Cheng    susceptible to dimensional alterations owing to their
            et al.  loaded BMSCs-derived exosomes (BMSCs-Exos)   propensity to absorb water and subsequently swell. This
                [71]
            into GelMA hydrogel and found that the GelMA hydrogel   can potentially lead to the loss of the meticulously designed
            provided a good carrier for exosomes and facilitated   structural integrity, underscoring the importance of
            chondrogenesis in vitro and cartilage regeneration in vivo.   managing and predicting the swelling behavior of GelMA-
            Similarly, Guan et al.  observed that BMSCs-Exos-loaded   based materials in practical applications.
                            [72]
            GelMA hydrogel could significantly boost the formation of   Overall, there are also challenges with using 3D-printed
            new cartilage in rats with joint defects by modulating the   GelMA-based biomaterials in cartilage engineering, such
            immune microenvironment.                           as its limited mechanical strength compared to native
               Although there are not many studies on the combination   cartilage tissue and the control of degradation rate. Further
            of  exosomes  and  3D-printed  GelMA-based  biomaterials   research is needed to optimize GelMA-based materials for
            in articular cartilage tissue engineering, exosome-loaded   cartilage engineering applications.
            GelMA hydrogel scaffolds still represent a promising
            strategy for promoting cartilage regeneration, especially
            when combined with 3D printing technology.         7. Summary and prospects
               Nevertheless, the development of active inks that offer   Cartilage repair presents a significant clinical challenge
            fitting environments to direct the healing process remains   today. Tissue engineering offers potential solutions, but
            a significant challenge. Still, it is important to consider   traditional strategies prove insufficient for constructing
            overcoming the limitations by determining the effective   complex, multi-layered tissues like articular cartilage. 3D
            dose, controlling the release of growth factors, and   printing technology makes it possible to overcome these
            managing any potential side effects.               challenges, with GelMA emerging as an exceptional ink for
                                                               3D printing.
            6. Limitations of 3D-printed GelMA-based              GelMA  boasts  numerous  advantages  for  cartilage
            biomaterials in articular cartilage tissue         tissue  engineering.  Its  mechanical,  swelling,  and
            engineering                                        lubricating  properties  closely resemble  those of  natural
                                                               cartilage, making it a good candidate for cartilage
            While GelMA-based biomaterials offer numerous benefits   regeneration.  GelMA promotes  chondrocyte  adhesion,
            for application in  articular cartilage tissue engineering,   proliferation, and stem cell chondrogenesis, thereby
            they do possess certain limitations.
                                                               maintaining  chondrocyte  phenotypes.  Moreover,
               Firstly, GelMA-based biomaterials demonstrates   the  high-degree  modifiability  and  adaptability  of
            significant potential as an ink for cartilage repair, yet it   GelMA diversify its applications. Due to its physical


            Volume 9 Issue 6 (2023)                        252                         https://doi.org/10.36922/ijb.0116
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