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International Journal of Bioprinting                                 3D bioprinting for organoid-derived EVs




            genome editing in correcting disease-associated genetic   Researchers have made significant progress in
            defects. 75,76  These advances highlight the important role   creating artificial vascular networks using bioprinting
            of PDOs in precision medicine and provide a platform   techniques, enabling the generation of intricate tissue
            to study disease progression, genetic disorders, and   structures. 78  Additionally,  innovative  bioprinting
            personalized treatment strategies.                 approaches have been developed to transfer spheroids
                                                               into self-healing support hydrogels at high resolution,
            2.3.2. 3D bioprinting of patient-derived organoids   allowing for the precise manipulation of single spheroids
            PDOs have become essential in advancing precision   and organoids.  The development of aspiration-assisted
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            medicine,  particularly  in  tumor  immunology  studies.   bioprinting and multi-material bioprinters has improved
            These 3D tissue cultures have enabled the successful   the precision and versatility of bioprinting, enabling the
            propagation of human tumor biopsies in vitro, enhancing   construction of high-cell density and heterogeneous
            our comprehension of the tumor microenvironment    tissue models. 80,81  Moreover, the utilization of bioinks
            and genetics.  However, conventional PDO models face   containing nanoparticles has enhanced the mechanical
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            several challenges.  While  most  tumor PDOs  replicate   strength and functionality of bioprinted tissues,
            the genetic composition of the parental tumor in early   supporting the long-term expansion and improved drug
            passages, the extent of genetic drift or the proportion of   testing of organoids.  Furthermore, the incorporation
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            genetically stable cells in later passages remains unclear.    of organoid-forming stem cells into centimeter-scale
                                                          6
            Additionally, the lack of endogenous tumor-associated   tissues through bioprinting has facilitated studies on
            stromal components is another significant limitation of   organ development, disease progression, and potential
            current organoid methods.                          therapeutic  interventions. 83  Temperature-controlled
               Recent advances in 3D bioprinting have shown    printing platforms have been utilized to enhance cell
            promising advancements to address these challenges.    viability and successfully fabricate complex tissue
            Table 2 summarizes and compares the notable        structures, showcasing the potential of 3D printing
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            advancements. 3D bioprinting techniques enable precise   technology in tissue engineering.  These advancements
            layering  of cells,  biomaterials,  and biochemical  factors,   not only support the long-term expansion and improved
            facilitating the creation of complex tissue structures that   drug testing of PDOs but also enable the recapitulation of
            closely resemble in vivo environments.  This technology   the real structure and function of organoids, addressing
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            can play pivotal roles in overcoming issues in organoid   critical challenges faced by conventional PDO models.
            construction, including incorporating vascular structures,   The advancements in 3D bioprinting have opened new
            immune cells, achieving precise spatial architecture, and   horizons in disease modeling and precision medicine.
            scaling up to tissue sizes.                        Researchers have successfully developed patient-specific



            Table 2. Advances and innovations of 3D bioprinting.

             Technique            Advancement                Significance                               Ref.
             Vascular network bioprinting  Creation of intricate tissue structures   Enables generation of complex vascularized tissues, improving   78
                                  using bioprinting          tissue engineering outcomes
             Precise spheroid manipulation  Transfer of spheroids into self-healing   Allows precise manipulation of spheroids and organoids,   79
                                  hydrogels at high resolution  creating high-cell density, heterogeneous models
             Aspiration-assisted bioprinting  Enhanced precision and versatility in   Improves precision and versatility of bioprinting, constructing   80
                                  biofabrication             high-cell density, heterogeneous models
             Multi-material bioprinting  Simultaneous printing of multiple cell   Creates heterogeneous tissue structures, enhancing the   81
                                  types                      complexity of bioprinted models
             Nanoparticle-enhanced bioink   Development of bioinks containing   Increases mechanical strength and functionality of tissues,   82
             printing             nanoparticles              supporting long-term expansion and improved drug testing
             Large-scale tissue bioprinting  Printing of organoid-forming stem cells  Facilitates studies on organ development, disease progression,   83
                                  to form large tissues      and therapeutic interventions
             Temperature-controlled   Use of temperature-controlled printing   Successfully fabricates complex tissue structures,   84
             bioprinting          to enhance cell viability  demonstrating the potential of 3D printing in tissue
                                                             engineering
             Abbreviation: 3D, three-dimensional.


            Volume 10 Issue 5 (2024)                       103                                doi: 10.36922/ijb.4054
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