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International Journal of Bioprinting                                   Biofabrication for islet transplantation




            and their profound implications in  islet  transplantation.   including 3D bioprinting, have the potential to establish
            Notably, remarkable strides toward islet transplantation have   high-throughput manufacturing systems that allow rapid
            been made in recent decades, predominantly because of the   and efficient production. By incorporating biomaterials
            remarkable progress achieved in biofabrication technology.   with diverse mechanical and biochemical characteristics,
            Many biofabrication techniques have been introduced by   bioprinting technology can faithfully mimic the native
            researchers who employed diverse biomaterials as carriers for   pancreatic microenvironment and optimize the conditions
            efficient islet delivery. The primary focus of these studies was   for islet survival and functionality. Consequently, this
            to enhance islet engraftment, fortify immune protection, and,   high-throughput bioprinting  technology  holds promise
            ultimately, prolong graft viability. To address the challenge   for meeting the clinical demand for large-scale islet
            of the immune response and optimize cell survival, it is   encapsulation  constructs  and  for  advancing  the  field  of
            imperative for researchers to prioritize the development of   islet transplantation. Combining the strengths of dECM
            encapsulation technology as a viable means of islet delivery.   and bioprinting technology offers an opportunity to
            Although ongoing clinical trials are assessing the efficacy of   enhance the efficacy and long-term outcomes of islet
            microencapsulated islets, sustained blood glucose control   transplantation, bringing us closer to curing diabetes.
            over an extended period has not yet been achieved. The
            fundamental  objective  of  islet  encapsulation  is  to  mitigate   Concurrently, there is an imminent need for more
            the risk of immune rejection of transplanted islets while   alternative cell sources. Multiple cell types have been used
            effectively emulating the pancreatic microenvironment,   in islet delivery systems to generate insulin-producing
            thereby facilitating insulin secretion and enabling the uptake   cells. Although cell lines present advantages in terms of
            of vital nutrients for sustained survival.         ease of handling and mass production, they present notable
                                                               challenges in clinical trials and are inherently constrained
               The careful selection of appropriate biomaterials is   in terms of their capabilities. The use of primary islets
            of paramount importance for establishing an optimal   obtained from suitable donors poses inherent challenges,
            microenvironment  for islets,  which  is  crucial  for   including those associated with allograft transplantation
            the transplantation process. The microenvironment   and limited availability. Consequently, a promising avenue
            encompassing the islet graft exerts a pivotal influence,   in this domain is the utilization of insulin-producing cells
            owing to a multitude of factors. A particularly promising   differentiated from human or patient-derived iPSCs. This
            approach for islet transplantation involves the utilization   approach offers unrestricted access to organs and facilitates
            of dECM, which offers distinct advantages and specialized   donor-independent transplantation. This approach
            characteristics. Through the removal of cellular components   offers unrestricted access to organs and facilitates donor-
            while retaining the native ECM structure, the dECM serves   independent transplantation, while the improvement of
            as a biocompatible scaffold that facilitates the survival and   differentiation efficiency through established protocols is
            functionality of islets. The integration of dECM in the context   still  ongoing.  Although  several  differentiation  protocols
            of islet transplantation enhances the biocompatibility of islet   have been established, the implementation of this approach
            grafts, diminishes the risk of immune rejection, and fosters a   is still in progress, with challenges such as difficulties
            favorable microenvironment conducive to sustained survival   in improving the efficiency of differentiation [100–103] .
            and insulin production in islets. Extensive research focused   The iPSC differentiation technique presents technical
            on dECM derived from pancreatic tissue has successfully   complexities and financial challenges that require further
            validated its inherent characteristics, particularly regarding   attention [104,105] . Nevertheless, differentiation techniques
            the intricate interplay between islets and their surrounding   to generate insulin-producing cells are expected to play a
            environmental cues, including viability, insulin secretion,   critical role in future research on islet transplantation.
            and glucose responsiveness. Furthermore, dECM can be
            further  functionalized  to  enable  the  targeted  delivery  of   Acknowledgments
            bioactive molecules, such as immunomodulatory factors or
            angiogenic agents, thereby offering additional enhancements   None.
            to the therapeutic outcomes of islet transplantation.
                                                               Funding
               The choice of the fabrication method is of significant
            importance in the development of a comprehensive islet   This work was funded by the National Research Foundation
            delivery system that encompasses both biomaterials   of South Korea (NRF) grant from the Ministry of Science
            and cells. The versatile nature of the 3D bioprinting   and ICT (No. 2021R1A2C2004981) and supported by the
            technology enables  the  use of  multiple  biomaterials   Korean Fund for Regenerative Medicine funded by the
            and facilitates the creation of constructs with tailored   Ministry of Science and ICT and Ministry of Health and
            properties. Furthermore, biofabrication technologies,   Welfare (21A0104L1, Republic of Korea), as well as the

            Volume 9 Issue 6 (2023)                        408                        https://doi.org/10.36922/ijb.1024
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