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Table 1 Summary of liver microsystems in vitro

From: Liver microsystems in vitro for drug response

Engineering method

Drug response study

Advantage

Disadvantage

Hepatocyte type

Engineered ECM

Soft lithography [5,6,7,8,9,10,11]

- Drug hepatotoxicity [5, 9]

- Drug-drug interactions [5]

- Enzyme induction [5]

- High cell interaction between different cells in 2D coculture

- Low relevance to liver lobule anatomy

- Lack of 3D morphology

- Primary cell [5,6,7,8, 10, 11]

- Cell line [9]

- Collagen [5,6,7,8,9,10,11]

DEP cell patterning [12,13,14,15]

- Enzyme induction [13]

- Direct cell patterning

- Buffer or hydrogel with small conductivity

- Cell line [12,13,14,15]

- Agarose [12, 15]

- Collagen [13]

- PEG hydrogel [12]

Hydrogel photolithography [19,20,21,22]

- Enzyme induction [21]

- Patterning heterogeneous biomaterials

- High resolution

- Damages by UV radiation and free radical

- Primary cell [20]

- Stem cell [21]

- Cell line [19, 22]

- Gelatin [22]

- GelMA [19, 21]

- PEG hydrogel [19]

- PLA [20]

Hydrogel micromolding [23, 28,29,30]

- Cancer therapy [23]

- Drug hepatotoxicity [28]

- Metabolic function [29]

- Patterning heterogeneous biomaterial

- Poor flexibility to complicated geometry

- Primary cell [30]

- Stem cell [29]

- Cell line [23, 28]

- Fibrin gel [30]

- GelMA [28]

- PEG hydrogel [23]

- PLGA [23]

- POMaC [29]

3D bioprinting [24, 25, 35,36,37,38,39,40,41]

- Drug hepatotoxicity [25]

- Enzyme induction [25, 36, 37]

- Transplantation [41]

- Patterning heterogeneous biomaterial

- Directly printing biomaterial in 3D space

- Large-scale printing

- Large pressure and shear stress during the printing

- Primary cell [24, 25, 37, 41]

- Stem cell [38]

- Cell line [24, 36, 40]

- Alginate [40]

- Collagen [24, 40]

- Gelatin [36]

- GelMA [24, 40]

- Matrigel [40, 41]

- NovoGel [25]

- PEG hydrogel [40]

Microfluidics [40,41,42,43,44,45,46,47,48,49,50,51,52,53,54,55]

- Drug hepatotoxicity [46, 48, 51, 52, 58, 59, 61, 68,69,70]

- Drug metabolism and pharmacokinetics [67,68,69,70]

- Drug-drug interactions [52, 59, 60]

- Enzyme induction [48, 53, 54, 59, 60, 67, 69]

- Liver immune [53, 56, 60]

- Liver zonation [36, 50, 59]

- Perfusion culture as in vivo

- Automation

- Small sample volume

- Gradient generator

- Closed culture environment

- Primary cell [46,47,48,49, 53, 56,57,58,59,60,61]

- Stem cell [54,55,56]

- Cell line [47, 50,51,52, 55, 56, 60, 67,68,69,70]

- Agarose [51]

- Collagen [48,49,50,51,52,53, 56, 59, 68,69,70]

- Fibronectin [67]

- Gelatin [51]

- PEGDA [54]