Table A2.
Biomaterials that have been investigated for 3D models for studying liver cancer.
| Biomaterial | Type | Model | Cells | Application | Results | Source, Year |
|---|---|---|---|---|---|---|
| Synthetic | ||||||
| PEG (8-arm PEG-SH) | Spheroid | HepG2 | Spheroid formation and recovery due to polymer biodegradation with cysteine | Increased cell function (albumin and urea) | Moriyama et al., 2016 [159] | |
| Polystyrene (PHP) | Tissue Engineered (TE) | HepG2 | Structure, function and cytotoxicity study (methotrexate) | TME bio-mimicry: bile duct formation and higher drug resistance | Bokhari et al., 2007 [172] | |
| TEOS–PDMS | TE | HepG2 | Function under dynamic flow | TME bio-mimicry: increased proliferation and aggregation capacity, higher albumin synthesis than in 2D cultures | Kataoka et al., 2005 [176] | |
| PVA | TE | HepG2 | Function under dynamic flow | TME bio-mimicry: higher albumin synthesis than in 2D cultures | Kataoka et al., 2005 [176] | |
| Biologic | ||||||
| Collagen | Hetero-spheroid | HepG2 and stromal fibroblasts | Cytotoxicity study (DOX) | TME bio-mimicry: cell function (P450 activity) and increased drug resistance | Yip et al., 2013 [161] | |
| Alginate | Spheroid | MHCC97L HCCLM3 | Metastatic mechanism study | TME bio-mimicry: increased cell maturity, in particular in metastatic cells MHCC97L | Xu et al., 2013 [143] | |
| Alginate/chitosan blend | Spheroid | PLC/PRF/5 HepG2 | Cytotoxicity study (DOX) | TME bio-mimicry: increased malignancy and drug resistance | Leung et al., 2010 [158] | |
| Silk fibroin | TE | HepR21 HepG2 | TME study | HepR21 showed irregular aggregation and higher proliferation capacity than HepG2 | Kundu et al., 2013 [177] | |
| Silk fibroin/chitosan | TE | HepG2 | Liver regeneration | Mechanical properties controllable, good cell proliferation | She et al., 2008 [181] | |
| Silk fibroin-lactose (Lac-CY-SF) | TE | FALC-4 | Liver regeneration | Functional gene expression not found using collagen | Gotoh et al., 2011 [175] | |
| Composite | ||||||
| Decellularized human liver tissue | TE | LX2 Sk-Hep-1 HepG2 |
Liver regeneration | Bio-compatibility and ECM remodeling | Mazza et al., 2015 [179] | |
| Alginate/decellularized liver ECM | Bead | HCCLM3 | Metastatic mechanism study | TME bio-mimicry: Increased cell viability and metastatic potential due to liver ECM | Sun et al., 2018 [170] | |
| Alginate/gelatin microspheres | Spheroid | HepG2 | Formation of spheroids with defined size by microsphere dissolution with MMP-9 | Spheroids of 200 µm with no necrotic core | Lau et al., 2012 [157] | |
| Bioartificial | ||||||
| pNIPAAm-co-gelatin | Spheroid | Hepa/8F5 | Cytotoxicity study (tamoxifen and acetaminophen) |
Increased cell function (albumin CYP3A4 activity, ammonia removal) and drug resistance | Sarkar et al., 2017 [160] | |
| Collagen-PEG/succinic acid | TE | HepG2 | Effect of material stiffness | Higher cell cluster size and infiltration capacity in softer hydrogels | Liang et al., 2011 [178] | |
| PVA/gelatin | TE | HepG2 | Cell migration | TME bio-mimicry: tissue-like cell organization, possibility to visualize migratory phenomena | Moscato et al., 2015 [180] |