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International Journal of Bioprinting                                     Bioprinting of β-islet-like constructs



            pancreas or pancreatic islets from human or animal   classified 3D bioprinting approaches within the general
            sources, has always been a viable option to restore active   technology field of 3D printing into different categories
            insulin secretion in T1D [48–50] . Allograft transplantation   based on standard document ISO/ASTM 52900:2015-12
            has limitations because of the shortage of pancreatic   for additive manufacturing techniques, material jetting, vat
            tissue  donors.  The transplantation  of xenogeneic  islets   photopolymerization, and material extrusion (Figure  2B
            has often been studied to overcome donor scarcity. Islet   and Table 2).
            tissue from different species has been explored. Porcine
            pancreatic islets have been addressed because of their   3.1. Material jetting printing
            insulin structural similarities with human ones and other   Since its inception, 3D material jetting printers have
            reasons. Immune rejection after transplantation is one of   evolved to print various materials and continuously
            the major challenges in this issue. The encapsulation of   increase resolution, which, when it comes to inkjet, refers
            β-islets with biocompatible polymers has been developed   to the droplet size itself . The droplets are measured in
                                                                                  [67]
            to  attenuate  the  complications  of  immunosuppressive   the picoliter to nanoliter range in volume and contain
            agents. This encapsulation can supply physical hindrance   the  biological  medium  desired  for  the 3D  construct [68,69] .
            to transplanted islets and prevent immune rejection by the   Based on the mentioned classification, in addition to the
            recipients . One possible solution to the donor shortage   methods including piezoelectric/thermal inkjet, acoustic
                    [51]
            is the generation of β-cells or islet-like tissues from human   wave jet, and electrohydrodynamic jet, which is regulated
            MSCs [52,53] , human embryonic stem cells (hESCs) [54–56]  and   by controlling droplets based on the nozzle function, the
            induced pluripotent stem cells (iPSCs) (Figure 1C) [57,58] .   laser-assisted bioprinting (LAB) or laser-induced forward
            Directed cell differentiation  and  xenograft  models  alone   transfer  (LIFT)  technique  is  belonged  in  the  material
            cannot solve the lack of donors, the three-dimensional (3D)   jetting bioprinting category also . The  piezoelectric
                                                                                           [66]
            structure is also necessary. A functional artificial pancreas   jetting relies on signals translated to vibrations within the
            that resembles the original tissue can become a reality with   printer head. The vibrations break the medium into little
            3D tissue bioprinting, a revolutionary development in   droplets ready for printing . Meanwhile,  the thermal
                                                                                      [70]
            recent years. This technology can provide everything that   inkjet dispenses droplets by increasing the temperature
            may be needed, even for clinical use. However, choosing   of the heating element to approximately 200°C, causing a
            the right printing technology and using the right cells and   bubble that pushes the bioink out from the printer head.
            scaffolds can significantly influence the results.  Despite the high temperature, the heat has (theoretically)
                                                               little impact on the viability of the cells within the bioink .
                                                                                                           [71]
            3. 3D Bioprinting                                  Instead, in practice, the energy  is  dispersed  as  bubbles,
                                                               with little to no heat energy ever reaching the cells or the
            In the context of tissue engineering and regenerative   hydrogel itself, which is mostly true, whereas acoustic wave
            medicine, the terms  biofabrication and  bioprinting,   jetting utilizes acoustic energy to create droplets , and in
                                                                                                     [72]
            which indicate the integration or participation of biology   electrohydrodynamic jetting, droplets are formed based
            with other fields of science, are frequently mentioned.   on electric voltage. LIFT is a form of printing that does not
            Biofabrication is  defined as  “the automated generation   require direct contact with the print surface. It works by
            of biologically functional products with a structural   propelling hydrogel droplets containing suspended cells onto
            organization from living cells, bioactive molecules,   a growth surface. The method requires a laser transparent
            biomaterials,  cell  aggregates  such  as  microtissues,   print ribbon and a receiving substrate. There are two layers
            hybrid cell-material  constructs  through bioprinting or   within the print ribbon for propelling . A sacrificial layer
                                                                                             [73]
            bioassembly” . Bioprinting technology is an innovative   is lost during the process, and a material layer is meant to
                      [59]
            process in advanced tissue engineering that allows the   be a viable postprint. The sacrificial layer absorbs the laser
            layer-by-layer arrangement of a wide array of cell types,   energy and evaporates, and through the expansive power of
            biomaterials, and bioactive factors in precise order . This   evaporation, the material transfer layer is ejected onto the
                                                    [60]
            emerging technology has introduced promising prospects   substrate. The amount of projected material is controlled
            in regenerative medicine to simulate the native tissue   by the laser energy profile. To lower the kinetic energy by
            environment for fabricating clinically applicable live tissues   the propulsion, the substrate is coated with an additional
            and in vitro 3D models for screening therapeutics [61,62] .   layer of hydrogel. LIFT is the only printing approach that
            Bioprinter cartridges contain a combination of various   offers direct visualization of cells both before and after
            types of cells in hydrogel biomaterials as scaffold   printing. Unlike other inkjet printing methods, which use
            precursors, which are actually called bioinks [63–65] .   a nozzle, LIFT does not need it and can thus print various
            Although  different  classifications  have  been  described   substances that would otherwise clog the nozzle. Hakobyan
            for different types of bioprinting methods, Lee  et  al.    et al.  have generated a 3D pancreatic cell spheroid which
                                                        [66]
                                                                   [74]
            Volume 9 Issue 2 (2023)                        260                     http://doi.org/10.18063/ijb.v9i2.665
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