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] |