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




            and reproducible are essential for clinical applications.   5. Conclusion and outlooks
            Additionally, regulatory guidelines need to be established
            to govern the production and use of bioprinted EVs in   The integration of 3D bioprinting with EVs and organoids
            clinical settings.                                 represents a cutting-edge approach with tremendous
                                                               potential in precision medicine. Overcoming technical
               Optimizing the enrichment of EVs is another critical   challenges, standardizing production processes, optimizing
            challenge. Current methods for EV isolation, such as   EV enrichment, and conducting further research to
            ultracentrifugation, size-exclusion chromatography, and   validate their efficacy are crucial steps in harnessing the
            immunoaffinity  capture,  often  result  in  low  yields  and   full potential of 3D-bioprinted OEVs for personalized
            purity. Enhancing these techniques or developing new   medicine and regenerative therapies. Continued research
            methods to increase the efficiency of EV enrichment is   and  innovation  will  pave  the  way  for  new  therapeutic
            necessary. Additionally, understanding the heterogeneity   avenues, improving the treatment of complex diseases and
            of EV populations and identifying therapeutically relevant   advancing personalized medicine. As this field progresses,
            subtypes are crucial for optimizing enrichment processes.  the significant potential of 3D-bioprinted OEVs will
               Continued advancements in 3D bioprinting technology,   become increasingly apparent,  offering  promising
            including improvements in printer resolution, speed,   solutions for various medical applications and enhancing
            and bioink formulations, are essential for the successful   patient outcomes in the future.
            integration of EVs with bioprinted organoids. Innovations
            such as multi-material printing and real-time monitoring   Acknowledgments
            of the bioprinting process can enhance the precision and   All figures were created using BioRender.
            functionality of bioprinted constructs. Furthermore,
            developing bioinks that can support the encapsulation   Funding
            and controlled release of EVs will be crucial for creating
            effective therapeutic constructs.                  This work was supported by the National Research
                                                               Foundation of Korea (NRF) funded by the Republic of
               While the bioprinted EVs, particularly OEVs,    Korea government (2022R1C1C1009606), and the Basic
            show  promising  therapeutic potential  in  various fields,   Science Research Program through the National Research
            further  research  is  necessary  to  validate  their  efficacy   Foundation of Korea (NRF) funded by the Ministry of
            across various therapeutic applications. OEVs may offer   Education (2022R1I1A1A01071265).
            advantages over traditional EVs in terms of quantity and
            physiological effects, making them more suitable for   Conflict of interest
            therapeutic applications. By exploring a broader range
            of 3D-bioprinted OEVs in different therapeutic areas   The authors declare they have no competing interests
            such as chronic inflammatory diseases, researchers can
            uncover new applications and maximize the utility of   Author contributions
            bioprinted EVs.                                    Conceptualization: Mi-Kyung Oh, Kyung-Rok Yu
               Despite the promising prospects, research on    Writing – original draft: All authors
            3D-bioprinted OEVs is still limited and their application   Writing – review & editing: Mi-Kyung Oh, Kyung-Rok Yu
            as a therapeutic tool remains largely unexplored. The
            potential  of  3D-bioprinted  OEVs  in  revolutionizing   Ethics approval and consent to participate
            biomedical research and providing new therapeutic   Not applicable.
            avenues for complex diseases, particularly inflammatory
            conditions, is substantial. As 3D bioprinting technology   Consent for publication
            advances and multifunctional integrated organoids are
            developed, the ability to simulate the human body’s   Not applicable.
            physiological environment and functions  in vitro will
            improve. These integrated organoids can be used to study   Availability of data
            complex  disease mechanisms, test drug efficacy  and   Not applicable.
            toxicity, and develop personalized treatment strategies. The
            ability to extract more effective OEVs from these advanced   References
            models will meet the demands of disease treatment and
            showcase the significant potential of 3D-bioprinted OEVs   1.   Karami Fath M, Azami J, Jaafari N, et al. Exosome application
            in benefiting patients.                               in treatment and diagnosis of B-cell disorders: leukemias,


            Volume 10 Issue 5 (2024)                       112                                doi: 10.36922/ijb.4054
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