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



            field.  HA  and  alginate  solutions  encapsulating  islet  cells   crosslinker PEGDA. Several scholars have confirmed that
            showed high viability and insulin secretion [121] . In a study,   merging collagen with other basement membrane proteins
            a combination of HA and collagen, instead of alginate   improves pancreatic islet maintenance and function.
            hydrogels, was used for transplanting islets and preventing
            immunogenicity [122] . Cañibano-Hernández et al. [123]  showed   4.1.5. Gelatin hydrogels
            that HA-alginate hybrid microcapsules reduce apoptosis   Gelatin  is  a  natural  polypeptide  conceived  from  the
                                                                                 [131]
            and  increase  β-cell  viability.  Nevertheless,  the  ability  of   hydrolysis of collagen  . Scholars have extensively used
            cells to produce insulin in response to glucose induction   gelatin and its mixtures due to their biocompatibility,
            was unaltered. Based on the available evidence, it seems   biodegradability, and low immunogenicity for pancreatic
            that the HA-encapsulated islets were less immunogenic   islet bioengineering. In the ECM of adult human pancreas,
            than the alginate ones.                            collagen is the major component of the basement
                                                               membrane; therefore, gelatin could be used instead of
            4.1.4. Collagen hydrogels                          it. Mechanical strength is a vital property of artificial
            Collagen is a fibrillar protein abundant in the ECM of the   pancreatic tissues. Gelatin alone cannot accomplish this
            connective tissues of mammals [124] . The physical integrity   paragon. In this regard, various polymers have been
            and mechanical strength of tissues depend on the collagen   combined with gelatin. Gelatin with polyglycolic acid
            content and the degree of its mineralization. Collagen   (PGA) scaffolds has been used for encapsulating mice
            provides a network for migrating and attaching cells in the   pancreatic islets. Bioengineered islets were transplanted
            ECM [125] . The biological and biochemical characteristics,   into STZ-induced diabetic nude mice. The animals
            such as excellent biocompatibility, biodegradability, weak   maintained their normal blood sugar for up to four months
            antigenicity, and tensile strength, made collagen a useful   after transplantation, and the pancreatic islets kept their
            biomaterial and primary resource in tissue engineering and   potential for insulin secretion [132] . Gelatin methacrylate
            regenerative medicine [126,127] . Currently, most collagens are   (GelMA) is a photo-crosslinkable natural hydrogel
            extracted from animal sources, such as porcine, bovine, rat   material achieved by reacting methacrylic anhydride with
            tails, and others, and are applied as biomaterials in tissue   gelatin, which can optically crosslink in the presence of
            engineering and organ bioprinting. There are some general   a photoinitiator. Adding the methacrylamide functional
            physicochemical differences, such as thermal stability,   groups in GelMA allows the synthesis of a stable hydrogel
            gel formation time, and crosslinking density between   while retaining the cell-binding motifs of gelatin. Further,
            animal species, for hydrogel matrices; however, the viral   GelMA biofunctionality and its mechanical tunability
            and prion contamination, batch-to-batch diversity, and   cover the requirements of most tissue engineering
            immunogenicity of species-specific origins are the issues of   applications. Different cell types can easily  attach,
            concern [128,129] . Recombinant human collagen is considered   spread,  and  proliferate  in  this  context.  Additionally,  by
            a potential solution but recombinant collagen has not been   modifying the methacrylate functional group, we can
            produced on an industrial scale due to post-translational   control the hydrogel’s physical properties, such as porosity,
            issues [130] . Collagen and its hydrolyzed form (gelatin)   biodegradability, and swelling ratio, by adjusting the
            hydrogels can be crosslinked with photopolymerization,   degree of functionalization, and polymerization conditions
            and because of their physiological properties, few   can obtain excellent spatiotemporal control, allowing for
            attempts have been made to modify the collagen itself.   the fabrication of hydrogels with unique patterns, 3D
            Nonetheless,  because  of  limited  mechanical  properties,   structures, and morphologies.
            some experiments have been performed by combining
            chitosan and collagen, which seems to create a hydrogel   4.1.6. Matrigel®
            that easily maintains structural integrity while maintaining   Matrigel® is a protein combination secreted by the mouse
            the biological properties of collagen. Harrington et al. [122]    sarcoma cell line (Engelbreth Holm Swarm, EHS).
            demonstrated that using a hybrid hydrogel of collagen   Matrigel possesses most basement membrane components
            and HA, named under  HyStem-C, for allogeneic islet   in the ECM of connective tissues [133] . It mainly comprises
            transplantation has lower immunogenicity than alginate   laminins, type IV collagen, and nidogen. Owing to the
            hydrogel. Additionally, they found that the transplanted   positive effect of Matrigel on sustaining self-renewal and
            islets encapsulated in this hydrogel exhibited normal blood   proliferation of stem cells, it is widely considered for cell
            glucose levels for more than 1 year in outbred streptozotocin   culture [134,135] . Gerggio et al. [136]  demonstrated that Matrigel
            (STZ)-induced diabetic Sprague-Dawley rats. Based on   improved the proliferation of mouse embryonic pancreatic
            the company datasheet, HyStem-C is chemically defined   progenitors in 3D culture. Using Matrigel and pancreatic
            by three biocompatible components: thiol-modified HA,   progenitor cells, they produced hollow spheres or complex
            thiol-modified denatured collagen, and thiol-reactive   organoids to study the morphogenesis and differentiation


            Volume 9 Issue 2 (2023)                        265                     http://doi.org/10.18063/ijb.v9i2.665
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