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International Journal of Bioprinting                                   Biofabrication for islet transplantation




            between islets and ECM using synthetic peptides and   of nutrients and oxygen for islet cells located at the center
            polymer scaffolds . VEGF within transplants stimulates   of the capsules . Encapsulation techniques can be broadly
                                                                          [25]
                          [16]
            angiogenesis, improves the viability of engrafted islets,   classified into two categories based on the size: micro-
            and enhances the duration of normalized glycemia in   and macroencapsulation. In microencapsulation, a small
            diabetic mice after transplantation [17,18] . Therefore, the local   number of islets are enclosed in tiny capsules, typically less
            delivery of proangiogenic factors may improve the clinical   than a millimeter in size. These microcapsules facilitate
            outcomes of islet transplantation.                 the rapid diffusion of nutrients and oxygen, leading to

               Co-culture of angiogenesis-supporting cells can   high rates of islet survival because the favorable surface
            also promote network growth around or within the   area-to-volume ratio in the microcapsules is beneficial for
            transplanted islets. Among the endothelial cells, human   efficient mass transport. Nevertheless, microencapsulation
            umbilical vein endothelial cells (HUVECs) are widely   has limitations, such as the need for a large transplantation
            used for demonstrating this idea because of their ability   site to accommodate the necessary number of capsules, a
            to spontaneously assemble into tubular structures in an   suitable microvascular bed for immediate nutrient access,
            ECM . Several studies have examined the transplantation   difficulties in capsule removal, and insufficient long-term
                [19]
            of  pancreatic  islets  embedded  in  endothelialized   survival rates for functional islets to meet daily insulin
                                                                      [26]
            scaffolds [20,21] . A previous study showed that islets   demands .
            embedded in a HUVECs module returned diabetic         In contrast, macroencapsulation entails the entrapment
            mice to normal glycemia. HUVECs seeded on modules   of a higher quantity of islets inside larger capsules, commonly
            maintain the structural integrity of modular implants .   several millimeters in magnitude. These enlarged capsules
                                                        [22]
            Furthermore, facilitating the prompt sprouting of islet   allow the assembly of an elevated number of islets, leading
            endothelial cells post-transplantation could enhance the   to enhanced glycemic management and augmented
            engraftment process during the phase when the islets are   insulin secretion . Nevertheless, macroencapsulation
                                                                             [27]
            most susceptible. This could serve as an alternative that   faces certain obstacles, such as the challenge of ensuring
            depends solely on revascularization from the adjacent   proficient  exchange  of  nutrients  and  oxygen,  as  well
            tissue, a process that typically requires several weeks .  as the potential degradation of capsules over time .
                                                                                                           [26]
                                                     [23]
                                                               Despite the hurdles faced by both microencapsulation
            3. Biomaterial-based islet encapsulation           and macroencapsulation, the encapsulation approach
            strategies                                         still holds potential for islet transplantation and offers
                                                               a  possible  solution  for  sustained  glycemic  regulation  in
            Several biomaterial-based strategies have highlighted   patients with diabetes. Current research efforts are directed
            the crucial role of the extracellular environment in   toward enhancing the properties of biomaterial in order
            governing cellular behavior, emphasizing the need for   to overcome the constraints of existing technology and
            regenerative materials that provide biological cues to   ultimately improve the outcomes of islet transplantation .
                                                                                                           [28]
            cells . Biomaterials have emerged as promising solutions
               [24]
            to address medical challenges, and current investigations   The integration of islets within the selectively permeable
            have emphasized the significance of the extracellular   membrane  of  a macroencapsulation  device  has been
            milieu in modulating cellular behavior. Islet encapsulation   recognized as an effective approach for circumventing the
            technology is a biomaterial-based approach that involves   immune response, thereby enabling the transport of insulin
                                                                                          [28]
            enveloping islets within biocompatible materials and   from transplanted cellular entities . Macroencapsulation
            creating a supportive structure that closely mimics the   devices, typically ranging in size from millimeters to
            micro- and macroenvironments of native islets.     centimeters, offer the advantage of accommodating
                                                               multiple islets within a single construct, allowing for
            3.1. Islet encapsulation strategies                efficient encapsulation. The sizable dimensions of
            Recently, islet encapsulation has been widely used to   macroencapsulation devices afford remarkable adjustability
            provide not only mechanical and biochemical support but   because the membrane size, thickness, and pore size can
            also an immune barrier for encapsulated islets. During   be  precisely  tailored.  Thus, a  single  microencapsulation
            encapsulation, living cells are suspended in a biomaterial   device is able to accommodate the substantial number of
            designed to act as a transport barrier, allowing nutrients,   islets required for diabetes treatment.
            oxygen, and waste products to diffuse while providing a
            barrier to larger objects such as antibodies and immune   Thus, the utilization of macroencapsulation devices,
            cells. The three-dimensional (3D) matrix of the capsule   which act as physical barriers between transplanted
            fosters a supportive growth environment for islets,   cells and their recipients, has emerged as a promising
            preventing merging and interference with the availability   strategy to address specific challenges by eliminating the


            Volume 9 Issue 6 (2023)                        394                        https://doi.org/10.36922/ijb.1024
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