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International Journal of Bioprinting                                 Bioprinting organoids for toxicity testing




            3. 3D-bioprinted functional pancreas               or laminin mixtures did not affect the behavior of the cells
                                                               analyzed. A multilayer bioprinted structure of alginate
            3.1. Bioprinted pancreatic islet structure         bioink and polycaprolactone biodegradable polymer was
            Precise bioprinting technology allows for the orientation   encapsulated by beta cells (mouse insulinoma-6 [MIN-6])
            of islet cells and supporting cells and the recapitulation   (Figure 2C). In a study  using a mouse model with type
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            of the structural characteristics of natural islets. The islet   1 diabetes, the animals implanted with the bioprinted
            cells, after bioprinting, maintain their physiological state   structure showed a threefold increase in insulin secretion
            in  the  bioink  to  ensure  normal  function,  providing  not   and control of blood sugar levels 8 weeks after surgery
            only a new tool for the study of pancreas-related diseases,   (Figure 3).
            but also strong support for the development of diabetes
            treatment strategies.  Through in-depth exploration of   3.3. In vitro islet bioprinting process and AI-based
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            materials selection, cell distribution, scaffold design, and   automation control
            other factors in the construction process, this technology   The cutting-edge applications of in vitro islet bioprinting
            has made remarkable progress in the bioprinting of islet   and AI-based automation control have been explored. At
            structures, laying a solid foundation for future applications   present, in vitro bioprinting of islets has made remarkable
            in personalized medicine and tissue repair (Figure 2A).  progress, as evident by the successful construction of islet
                                                               structures, but challenges in maintaining the functionality
            3.2. Bioprinting of functional pancreatic islets   and stability of islets remain. In the future, it is expected
            The current 3D bioprinting technology can be used to   that a higher degree of functional maintenance of the
            construct the structure of the pancreatic islets, while   bioprinted  islets  can  be  achieved  by  optimizing  cell
            maintaining their functions. Precise cell orientation and   orientation, bioink formulation, and printing parameters.
            bioink optimization allow for the maintenance of islet cells’   Artificial intelligence-based automation control has
            normal endocrine functions during construction, including   great potential in the field of bioprinting. By establishing
            insulin secretion and glucose regulation. This achievement   intelligent models, the printing process can be monitored,
            promotes research in diabetes treatment, laying a solid   analyzed, and adjusted in real time to improve accuracy
            foundation for the development of personalized treatment   and controllability.
            strategies and biological tissue repair technologies, which
            will further improve therapeutic accuracy and efficacy. The   It has been demonstrated that artificial bionic islets
            3D-bioprinted pancreatic islets can promote insulin secretion   bioprinted from the stem cells derived from the pancreas
            over a long period of time, and the structure is implanted   of humans, rabbits, mice,  etc. can produce insulin based
            underneath the skin to prevent islet loss. Several recent   on blood sugar levels like what the normal human organs
            studies 44-46  have demonstrated the application of acellular   do.  In the long term, the 3D-bioprinted organs could
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            extracellular matrix to these islets and tumor models.   functionally replace the original pancreas. Different from
                                                               insulin  injections,  bioprinted  pancreas  can  continuously
               Pancreatic cancer is often used as a model for
            developing new treatments, and pancreatic cancer cell lines   produce insulin, significantly improving the quality of life of
                                                               patients. The pancreas contains many groups of specific cells,
            exhibit different behaviors in their respective inks. Cellink   and pancreatic cells generally refer to islet cells, including
            bioinks consist of alginate and nanofiber cellulose, and one   alpha cells, beta cells, pancreatic polypeptide cells, and delta
            of which is coupled to RGD peptide (Cellink RGD). GelXA   cells, which constitute the endocrine part of the pancreas and
            bioinks are composed of gelatin methacrylate, xanthan   are of great significance. At present, with the aid of computer-
            gum, and alginate, and one of which is coupled to laminins   aided design and computer-aided manufacturing, various
            (GelXA LAMININK+). These modifications were chosen   3D bioprinting technologies can create highly similar 3D islet
            because the expression of suitable integrin-like receptor   structures with advanced functions. In addition, pancreatic
            proteins is well described in malignant melanoma and has   cancer cells can also be bioprinted to build in vitro pancreatic
            been found to have an important role in tumor growth and   cancer model, which can be used to test anti-tumor drugs,
            progression. Matrigel is similar to the extracellular matrix   examine their adverse reactions, and aid in the personalized
            and is composed of type IV collagen, laminin, dentin,   treatment of pancreatic cancer patients.
            heparan sulfate proteoglycan, and growth factors. In
            Matrigel, the cells are able to spread, proliferate, and form   Tissue processing and cell culture during bioprinting
            dense networks throughout the construction process, while   dictate the quality of the resulting 3D-bioprinted structure.
            in alginate-based bioinks, the cells do not proliferate at all.   Taking  human  pancreas  as  an example,  the purpose  of
            In a bioink based on methacrylate gelatin, cells proliferate   cutting the tissue in the first step is to increase the contact
            in clusters. Surprisingly, modifying the bioinks with RGD   area between trypsin or collagenase and cells in the process



            Volume 10 Issue 1 (2024)                       129                          https://doi.org/10.36922/ijb.1256
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