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




                                                               the  personalization  of  treatment  strategies  based  on  the
                                                    self-renewal and self-organization in vitro. While organoids have advantages of mimicking the specific in vivo environment of individuals, they also suffer technical limitations such as scalability issues
                                                  Figure 1. Organoids for novel model systems. Organoids derived from primary tissue, embryonic stem cells (ESCs), or induced pluripotent stem cells (iPSCs) can model organ development through
                                                               characteristics of the patient’s own cells. 26
                                                                  Additionally, organoids have been instrumental
                                                               in establishing a model susceptible to T cell-mediated
                                                               tissue damage and have provided insight into the role of
                                                               autophagy in preventing inflammation-induced apoptosis
                                                               and preserving barrier integrity in chronic colitis. 12,13  These
                                                               3D structures can provide experimental manipulability
                                                               while maintaining biological complexity, bridging the gap
                                                               between traditional 2D cell cultures and animal models.
                                                               However,  traditional  organoid  culture  methods,  which
                                                               rely on self-organization, may result in creating diverse
                                                               morphologies and cell arrangements, which are different
                                                               from  that of real organs.  Integration of 3D  bioprinting
                                                               technology and organoid culture systems is needed as a
                                                               potential solution to address the limitations of traditional
                                                               organoid culture systems.

                                                               2.2. Principles of 3D bioprinting and organoid
                                                               formation
                                                               3D bioprinting technology enables the precise layering of
                                                               cells, biopolymers, and biomaterials to create complex and
                                                               accurate tissue structures. This technology significantly
                                                               enhances  the structural and functional fidelity  of
                                                               organoids, making them more anatomically precise and
                                                               physiologically relevant. By incorporating 3D bioprinting
                                                               with PDOs, researchers can overcome the limitations of
                                                               self-organization, achieving consistent morphologies and
                                                               cell arrangements closer to their native tissues. 27
                                                                  The principles of 3D bioprinting include the selection
                                                               of suitable bioinks, the design of printing protocols, and
                                                               the optimization of printing parameters to ensure cell
                                                               viability and functionality. Organoid formation through
                                                               3D bioprinting involves the encapsulation of stem cells
                                                               within a supportive matrix, followed by controlled
                                                      and a lack of vascular systems. Schematic created with BioRender.
                                                               differentiation and self-organization to form tissue-specific
                                                                       10
                                                               structures.  Here, we present common bioinks and various
                                                               bioprinting strategies.
                                                               2.2.1. Cell sources and bioinks
                                                               The success of 3D bioprinting organoids depends on the
                                                               development of appropriate bioinks that can support cell
                                                               growth and differentiation. Bioinks, which are composed
                                                               of biomaterials, live cells, and biomolecules, represent a
                                                               crucial component in 3D bioprinting processes (Figure 2A).
                                                                  Various materials such as alginate, agarose, gelatin,
                                                               fibrin, and Matrigel are commonly used as bioinks, each
                                                               offering unique properties such as biocompatibility,
                                                               mechanical strength, and bioactivity. 28–31  Both natural
                                                               polymers such as collagen, gelatin, and alginate and
                                                               synthetic  polymers  like  polycaprolactone  (PCL)  and
                                                               polyethylene glycol (PEG) are commonly used for


            Volume 10 Issue 5 (2024)                        99                                doi: 10.36922/ijb.4054
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