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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]