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International Journal of Bioprinting                               New challenges in liver tissue engineering




            Table 3. Liver cell transplantation for the treatment of liver disease
             Biomaterial  Cell type     Animal model  Highlights                                     Refs
             Inborn errors of metabolism
                                        Long Evans    –   Decrease in blood copper.
             HA scaffold  Fetal rat liver cells   Cinnamon rat   –   Significant reduction in total and direct bilirubin levels.  153
                                        (Wilson’s disease)  –   Increased albumin production.
             Collagen-coated   Rat hepatocytes  Gunn rat (Crigler–  –   Maintained decrease in serum total levels of bilirubin.  167
             microcarriers              Najjar disease)  –   Presence and persistence of conjugated bilirubin after 3–4 weeks.
             Acute liver failure
                                                      –   Improved survival.
             Decellularized rat   Human EpCAM+   Wistar rats + ALF   –   Improvements in ammonia, bilirubin, and albumin levels in   155
             liver scaffolds  cells     (D-GalN)        transplanted animals.
                                                      –   Reduction of prothrombin time in transplanted animals.
                          HLC-derived                 –   3D microenvironment supported hepatic differentiation of MSCs.
             Decellularized rat   mouse   NOD-SCID mice +   –   Increased survival (63%) in transplanted animals.   168
             liver scaffolds  mesenchymal   ALF (CCl )  –   Liver functions (albumin, transaminase, and bilirubin levels)
                                              4
                          stem cells                    improved after transplantation.
                                                      –   Reduction of transaminases levels and total bilirubin in transplanted
                                                        animals.
             PCL-PLA-PAAm-  Rat bone marrow   Sprague–Dawley   –   Histology of other relevant organs showed no toxicity associated to
             IGF-1/TNF-α   mesenchymal   rats With ALF   the scaffold.                               159
             scaffolds    stem cells    (D-GalN/LPS)
                                                      –  In vitro studies showed the differentiation potential of MSCs
                                                        cultured in the scaffolds.
                                        Nude mice +
             Col I and chitosan   L02 cells  ALF (radiation +   –   Increased survival of transplanted animals after 14 days.  162
             printed scaffold                         –   Decreased levels of ALT and AST.
                                        hepatectomy)
                                                      –   Increased survival in transplanted animals.
                                                      –   Significant reduction of transaminases levels in animals
                          Primary human   NOD/SCID with   transplanted with PHH-laden scaffolds compared to ALF animals
             Gel-HA scaffold                                                                         90
                          hepatocytes   ALF (APAP)      and ALF animals only treated with cells.
                                                      –   Reduction of oxidative stress and proinflammatory cytokines in
                                                        animals transplanted with PHH-scaffolds.
                                                      –   Increased survival (37%) in transplanted animals.
             Pullulan and   HepaRG      NOD/SCID mice   –   Human albumin remained stable in sera for 28 days.  117
             dextran scaffolds          with ALF (APAP)
                                                      –   Successful engraftment and survival of transplanted cells.
                                                      –   Increased survival in transplanted animals.
                                                      –   Reduced levels of transaminases and bilirubin levels in animals
                                                        transplanted with microbeads.
                          Rat primary   Sprague–Dawley rat
             Alg microbeads                           –   No sign of inflammation or adhesion was observed in treated   150
                          hepatocytes   + ALF (D-GalN)
                                                        animals.
                                                      –   Complete normal lobular architecture in transplanted animals after
                                                        1 week.
             Carboxymethyl-             BALB/c mice +   –   Increased survival of transplanted animals; survival was higher in
             hexanoyl chitosan   iPSC-HLC  ALF (thioacetamide   functionalized hydrogels containing HGF.  152
             HGF-releasing              overdose)     –   HLC delivered in hydrogels releasing HGF showed higher
             hydrogels                                  antioxidant and antiapoptotic activities that reduced necrosis.
             Mebiol TGP                 Wistar rat + ALF   –   Increased survival of transplanted animals.
             (PNIPAAm-PEG)  Rat hepatocytes  (D-GalN)  –   Reduction of transaminases and bilirubin levels after   151
             hydrogels                                  transplantation.
                                                      –   Higher survival of animals transplanted with cell-sheet HLC than
                                        Rag2/Il2rg double-
                          Human iPSC-   knockout mice +   those transplanted intrasplenically with HLC.
             Cell sheets                              –   Increased albumin levels in transplanted animals.  165
                          HLC           partial hepatectomy   –   Reduced transaminase levels in animals transplanted with cell-sheet
                                        (70%) + ALF (CCl )
                                                   4    HLC.
                                                                                                    (Continued...)


            Volume 10 Issue 3 (2024)                       131                                doi: 10.36922/ijb.2706
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