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Table 1 Summary of natural and synthetic materials used to culture and deliver cells for liver

From: Biomaterial-based cell delivery strategies to promote liver regeneration

Material Preparation Cell Type Effects Ref
Natural Materials
 Alginate Freeze drying + calcium crosslinking Rat hepatocytes In vitro: increased cell viability; hepatocyte spheroid formation; increased urea synthesis [80]
Freeze drying + calcium crosslinking Human hepatocytes and non-parenchymal cells In vitro: expression of mature liver enzymes; albumin secretion; liver organoid formation by 6 wks capable of drug metabolism [81]
Freeze drying + calcium crosslinking Porcine bone marrow-derived MSCs In vitro: expression of liver-specific genes and proteins; albumin and urea production; 56.7% of cells expressed cytokeratin-18 [82]
Gelation freeze technique Rat hepatocytes In vitro: cell viability maintained; albumin and urea production; fibronectin synthesis; no cell proliferation [83]
3D bioprinting + calcium crosslinking HepG2 cell line In vitro: liver-specific gene expression; recapitulation of lobule structure [84]
3D bioprinting + calcium crosslinking Mouse embryonic fibroblasts In vitro: formed hepatocyte-like colonies; In vivo: transplantation in damaged liver expressed liver-specific markers, survived for up to 28 d [85]
 Hyaluronate Photo-crosslinking Fetal liver cells In vivo: regeneration of tissue; prevention of jaundice and production of albumin; moderated liver fibrosis [86]
Esterification + hydrolyzation Mouse hepatocytes In vitro: established cell-cell contacts and albumin secretion in culture after 14 d; In vivo: survival of transplant for 35 d [87]
 Chitosan Freeze drying + fructose addition Mouse hepatocytes In vitro: formation of cellular aggregates; albumin and urea secretion [88]
Electrospinning Human hepatocytes In vitro: formation of aggregates, liver-specific function maintained; easy detachment for downstream applications [89]
 Collagen Coated onto dextran microcarriers Rat hepatocytes In vivo: survival and liver-specific function in rats lacking bilirubin metabolism [90]
Coated onto synthetic membrane Porcine hepatocytes In vitro: cell proliferation and synthesis of albumin and urea [91]
3D bioprinting HUH7 cell line In vitro: interconnected scaffold 3D geometry increased cell viability and proliferation; increased liver-specific function [92]
 Gelatin 3D bioprinting Rat hepatocytes In vitro: viability and liver-specific functions maintained for two months [93]
 Chitosan-gelatin Freeze drying HepaRG, LSEC, and HUVEC In vitro: HepaRG cells best viability and liver-specific function when cultured with LSECs; 3D culture improved results vs 2D [94]
Freeze drying Mouse hepatocytes In vitro: combination with alginate best albumin secretion; formation of spheroids; decrease in cell viability by 10 d [95]
 Cellulose Phase separation and lyophilization Rat hepatocyte In vitro: formation of hepatocyte spheroids; liver-specific functions; mature hepatocyte phenotype [96]
Infused into PLLA scaffold Human iPSC-derived hepatocytes In vitro: liver-specific cellular function [97]
 Heparin Photopolymerization + lithography Human ADSCs In vitro: increased albumin and glycogen storage; In vivo: liver retention and functional recovery [98]
Lipid conjugated + coated onto cells Human ADSCs In vivo: lowered AST/ALT levels, increased hHGF, reduced inflammation, cell retention [99]
 Natural ECM Decellularization +3D bioprinting HepG2, BMMSCs In vitro: induced stem cell differentiation; enhanced HepG2 cell function [100]
Decellularization + Ag nanoparticles HepG2 and EAhy926 cell lines In vivo: proliferation and HGF expression; lower aspartate transaminase and alanine transaminase plasma levels; lower liver homogenate nitric oxide levels [101]
Gelation of liver-derived ECM powder Primary human hepatocyte In vitro: high levels of albumin expression and secretion, ammonia metabolism, and hepatic transporter expression and function [102]
Decellularization (compared 4 methods) Human hepatic stem cells In vitro: lost stem cells markers; differentiated and maintained parenchymal phenotype for 8 wks [103]
Synthetic materials
 PLLA Dissolved in organic solvent Rat hepatocytes In vitro: formed spheroids with intercellular junctions; hepatocyte morphology and function preserved [104]
Particulate leaching method Rat hepatocytes In vivo: 1 wk. post-implantation: improved cell survival, glycogen storage capacity maintained [105]
3D printing + infused collagen Human iPSC-derived hepatocytes In vitro: viability; polarization; formation of bile canaliculi-like structures; natural ECM superior hepatocyte-specific function compared to PLLA scaffold [97]
Gas foaming Fetal liver cells, hepatic parenchymal cells In vitro: maintained cell viability; stimulated maturation of hepatic parenchymal cells [106]
 PCL Electrospinning HepG2 cell line In vitro: cells produced ECM; In vivo: support hepatic phenotype and function [107]
3D printing + collagen in channels Hepatocytes, HUVECs, human lung fibroblasts In vitro: improved survival of hepatocytes; albumin and urea secretion; formation of network with non-parenchymal cells [108]
 PCL-PLGA Multihead 3D printing Rat hepatocytes In vitro: improved cell adhesion and proliferation; high viability [109]
 PEG Photopatterning Hepatocytes, Lewis rats, NIH 3 T3-J2 In vitro: improved viability and liver-specific function over unpatterned controls [110]