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



            Table 3. Recently developed 3D-printed bioartificial pancreatic tissues
             Bioink material/ hydrogel  Islet donor/cell type  Printing technique  Details           Reference
             Alginate/methylcellulose  Rat islets  Indirect extrusion  The islets survived and insulin/glucagon was positive,   [114]
                                                                  but after glucose stimulation, increased apoptotic cell
                                                                  and reduced insulin secretion in printed islets versus
                                                                  free islets were seen.
             Alginate, Matrigel, gelatin,   Human islet, mouse islet,  Direct extrusion  High density of hydrogel decreased nutrient diffusion   [153]
             HA                 rat INS1E Β-cell                  within the gel and might hamper insulin secretion.
             Alginate           Mouse βTC-3 cells/rat   Coaxial extrusion  Formation of scaffold-free cell aggregates in the form   [152]
                                dermal fibroblast cells           of cylindrical strands could be fused together and
                                                                  keep viability and functionality of cells which secret
                                                                  insulin in tissue strands.
             Alginate/GelMA     Mouse islets, EPCs, Treg  Coaxial extrusion  Printing the core-shell construct, which keeps the   [154,155]
                                                                  mouse islets in the core and EPCs and Tregs in the
                                                                  shell as an immune protective layer, reduced insulin
                                                                  secretion after glucose stimulations.
             PLA/Fibrinogen     hESCs (SC-β-cells)  Indirect extrusion  Twelve weeks after implantation in subcutaneous   [146]
                                                                  space of non-diabetic SCID mice, serum insulin
                                                                  detection and C-peptide staining was positive.
             PLA                Human islets      Indirect extrusion  Platelet-lysate matrix (PLM) enriched with VEGF-  [156]
                                                                  loaded scaffold was implanted subcutaneously in the
                                                                  dorsum of nude mice, insulin was detected for up to
                                                                  22 weeks after transplantation.
             PLGA               Human islets      Indirect extrusion  Printed scaffold induced insulin secretion and   [147]
                                                                  endocrine gene expression compared to gels without
                                                                  3D scaffold.
             Pancreatic tissue dECM  Rat islets, human   Direct extrusion  Viability of pancreatic islets, which was printed in   [157]
                                islets, hiPSC, INS1 and           pancreatic tissue-derived decellularized extracellular
                                HUVEC                             matrix (pdECM), hydrogel was similar to that of
                                                                  nonprinted islets in 3D culture after 5 days, and
                                                                  coculture of HUVEC with pancreatic islets decreased
                                                                  apoptotic cell in the center of islets.
             PCL/pdECM          hPSC/MIN6-m9 cells  Micro extrusion  The insulin-producing β-cells printed in porous hybrid   [158]
                                                                  scaffold systems was better than the nonporous-type,
                                                                  3D-bioprinted pancreatic islet-like aggregates in
                                                                  terms of viability and function, and induced structural
                                                                  maturation and functional enhancement as well as
                                                                  polarization of M1 macrophage.
             Alginate/dECM and   Porcine islets, HUVEC   Coaxial extrusion  Insulin secretion upon glucose stimulation was   [159]
                                                                                          +
               Alginate/ Fibrinogen  and human MSCs               maintained, and the evidence of CD31  cells
                                                                  confirmed the potential formation of vessel-like
                                                                  structures.
             PCL/GelXA          INS1, HUVEC       Dual-extrusion  Heparin-functionalized PCL increased VEGF   [148]
             LAMININK-411 (Alginate,                              expression and cell adhesion, and commercial mixed
             GelMA, Laminin)                                      hydrogel induced β-cell proliferation and insulin
                                                                  secretion.
            HA, hyaluronic acid; GelMA, gelatin methacrylate acid; EPCs, endothelial progenitor cells; Treg, regulatory T cells; PLA, polylactic acid; hESCs, human embryonic stem
            cells; SCID, severe combined immunodeficiency; VEGF, vascular endothelial growth factor; PLGA, poly (lactide-co-glycolic acid); dECM, decellularized extracellular matrix;
            hiPSC,  human induced pluripotent stem cell; HUVEC, human umbilical vein endothelial cells; PCL, polycaprolactone; pdECM, pancreas decellularized extracellular matrix;
            hPSC, human pluripotent stem cell; CD, cluster of differentiation.
            material had the potential to support the survival of islets   trypsinization of tissue. The procedure aims to preserve the
            and improve the efficiency and insulin production in vitro   ECM while washing away cellular components and debris,
            and in vivo . The available biological scaffolds are limited   which effectively removes the scaffold immunogenicity .
                     [91]
                                                                                                           [92]
            to hydrogels and decellularized ECM (dECM). dECM can   Although hydrogel provides the initial structure, the cells
            be obtained by detergent washing and a process called   can only move and proliferate significantly as the hydrogel


            Volume 9 Issue 2 (2023)                        263                     http://doi.org/10.18063/ijb.v9i2.665
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