Recent Advances in Graphene Oxide-Based on Organoid Culture as Disease Model and Cell Behavior – A Systematic Literature Review

Figures & data

Table 1 Inclusion–Exclusion Criteria

Inclusion Criteria	Exclusion Criteria
Cell culture or organoid experimental studies	Abstract only and review article
Studies written in English	Off-topic studies
Cell culture or organoid intervention-related medium optimization with matrigel or alternative matrigel or graphene	Nothing medium optimization used matrigel or alternative matrigel or graphene
Measurement of cell behavior such as cell characteristics, cell proliferation, cell differentiation, and gene expression of combined graphene effects

Figure 1 Article Screening Process based on PRISMA Guidelines.⁵⁰

Figure 2 Graphene Oxide as Nanomaterial’s for Biomedicine Application.

Figure 3 Principle of Morphology, Proliferation, Differentiation, and Gene Expression in Cells Grow.

Figure 4 Principle of ECM for Cell Growth.

Figure 5 Potentials of graphene oxide for developing organoid Models.

Table 2 The Effects on Cell Characteristics for Cells or Organoid Culture

Class Materials	Materials	Cell Line/Primary Cell In Vitro	Applications	Cell Characteristics	Ref.
A. The Positive Effects on Cell Characteristics for Cells or Organoid Culture
Alternative Matrigel	Col-Ch	HUVECs	Tissue engineering and regeneration	Cells formed “spheric”.	[51]
	Se-EX-Ch-COL/TA	cECs	Tissue engineering and regeneration	cECS-like structures formation.	[52]
	PAMB-C-OHA	HUVECs, H9C2 cell	Tissue engineering and regeneration	Tubule-like blood vessel network formation for HUVECs and elongated shaped for H9C2.	[63]
	PUCL@CNT	NSPCs	Tissue engineering and regeneration	Neuron like structures formation.	[74]
	CPSN	BADSCs	Tissue engineering and regeneration	Myocardium-like structures.	[75]
	RSF/Mxene	HUVECs	Tissue engineering and regeneration	Tube formation produces more honeycomb-like structures.	[76]
	PLA- HA	HUVECs, monocyte	Tissue engineering and regeneration	Formed HUVECs- like structures.	[77]
	GG	PDLSCs, DPSCs	Tissue engineering and regeneration	Cells formed fibroblast-like.	[78]
	IGF1c-PHM	NSCs	Tissue engineering and regeneration	Neurospheres formation.	[79]
	Gelatine	Human skeletal muscle tissue	Therapeutic agent	Colony formed “spindle round”.	[81]
	Collagen	hPDLSCs, hBMSCs	Therapeutic agent	Cells formed “spindle”.	[82]
	Collagen	MDMs, BMDMs	Therapeutic agent	Formed mesenchymal and like structures “rosette”.	[83]
	Gelatine	CAFs, PDAC	Organoid models	Cells formed “spheroid”.	[89]
	GelMa	Bovine colon crypts	Organoid models	Formed new colonoids and can maintain viable models after 48 hours.	[90]
	Collagen	Fresh primary tumor	Organoid models	Phenotype cell of leader cells derived cancer cells differentiation.	[91]
	Chitosan-Pectin	HCT 116	Organoid models	Cells formed “spheroid”.	[92]
Alternative Matrigel	PEG	Human jejunal (J2, J3, J11) and duodenal epithelium (D109)	Organoid models	Maintaining phenotype cells of epithelial.	[93]
Matrigel	Matrigel	AT2S	Organoid models	Cell epithelial characteristics.	[94]
	Matrigel	Crypts (ileum), adult jejunum	Organoid models	Maintaining viable models.	[95]
	Matrigel	H9 ES cell	Organoid models	Formed neuroepithelium and rosette-like structures.	[96]
	Matrigel	Ileum biopsy	Organoid models	Cell epithelial characteristics.	[97]
Optimization Alternative Matrigel to Matrigel	Matrigel-Collagen-Manuka Honey	HUVECs, HMSCs	Tissue engineering and regeneration	Endothelial network formation.	[80]
	Matrigel-OEO-BG-PLGA-Gel	HUVECs	Tissue engineering and regeneration	Tubule-like blood vessel network formation.	[53]
	Matrigel-Gel-TCP/SC	HUVECs	Tissue engineering and regeneration	Tubule-like blood vessel network formation.	[54]
	Matrigel-EPO/CNP@FPH	HUVECs	Tissue engineering and regeneration	Tubule-like blood vessel network formation.	[55]
	Matrigel-dL-EG	PC12 cell line	Tissue engineering and regeneration	Neuron-like structures formation.	[56]
	Matrigel-AG-PCL	ADSCs, iSGCs	Tissue engineering and regeneration	Capillary-like network formation.	[57]
	Matrigel-BG-GO	EA-hy9.26 cell line	Tissue engineering and regeneration	Endothelial structure branch formation.	[58]
	Matrigel-MNSs-CNT-COOH	NSCs, C2C12 cells	Biosensing system	Neuromuscular junction’s formation.	[88]
	Matrigel - PSMPs@B	ISCs	Organoid models	Colon structure formation.	[98]
B. The Negative Effects on Cell Characteristics for Cells or Organoid Culture
Alternative Matrigel	Gelatine	CAFs, PDAC	Organoid models	The lack of maintaining phenotype cells.	[89]
	Collagen	Fresh primary tumor	Organoid models	The lack of cells is expressed.	[91]
	Chitosan-Pectin	HCT 116	Organoid models	Spheroid was irregular.	[92]
Matrigel	Matrigel	AT2S	Organoid models	The lack of maintaining recapitulate infection physiology.	[94]
Optimization Alternative Matrigel to Matrigel	Matrigel-Collagen-Manuka Honey	HUVECs, HMSCs	Tissue engineering and regeneration	Inhibited vessel formation.	[80]
	Matrigel - PSMPs@B	ISCs	Organoid models	Enhanced the damage to organoid models.	[98]

Table 3 The Graphene Oxide and Their Composite to Microenvironment in Cell Culture or Organoid Culture

Materials	Cell Line/ Primary Cell In Vitro	Applications	Cell Characteristics	Ref.
PANI–GO	SH-SY5Y, cortical neuronal cell	Tissue engineering and regeneration	Neurospheres formation.	[59]
CMCs-GelMa-GO-PLGA	HUVECs	Tissue engineering and regeneration	Tubule-like blood vessel network formation.	[60]
Ce-GO	HUVECs, HMSCs	Tissue engineering and regeneration	Spheroid formation.	[61]
EU/GL/TiO2	mESCs	Tissue engineering and regeneration	Embryoid bodies formation and colonies ESCs structures.	[62]
CH-GO	SH-SY5Y	Tissue engineering and regeneration	Cell phenotype like epithelial, cell growth is spread and elongated uniformly on the cell surface.	[64]
rGOM	ARPE-19, HCE-T	Tissue engineering and regeneration	Cells formed “polygonal”.	[65]
rGO-PCL	ADSCs	Tissue engineering and regeneration	Elongated spindle – like morphology.	[66]
adECM-PDA-rGO	NE-4C neuronal cell line	Tissue engineering and regeneration	Neuron like structures formation.	[67]
rGO-Mxene	MSU-1.1, HeLa, SH-SY5Y	Tissue engineering and regeneration	Maintaining cell phenotype.	[68]
SPI-SH-GA@PGO	HUVECs	Skin therapy	Tubule-like blood vessel network formation.	[70]
GO/rGO	MSCs	Therapeutic agents	Cells elongated with large nucleus (type of MSCs) and maintaining cell phenotype.	[84]
PEG-GO	MDA-MB-231, MDA-MB-436, MCF-10A	Cancer Therapy	Breast cancer cells metastated.	[86]

Table 4 Effects of Graphene Combination as Matrix Towards Proliferation, Differentiation, and Gene Expression

Materials	Cell Line/ Primary Cell In Vitro	Applications	Cell Behaviour				Ref.
			Cell Proliferation Ratio	Cell Differentiation	Gene Expression
					Upregulation	Downregulation
dL-EG	PC12 cell	Tissue engineering and regeneration	-	Neuron differentiation	-	-	[56]
BG/GO	rBMSCs, Raw264.7 cells	Tissue engineering and regeneration	0.7	Osteogenic and angiogenic differentiation	ALP, OCN, RUNX2, VEGF	-	[58]
CMCs-GelMa-GO-PLGA	MC3T3 cells	Tissue engineering and regeneration	>1	Osteoblastic differentiation	-	-	[60]
Ce-GO		Tissue engineering and regeneration	-	Angiogenic differentiation	HIF1α, VEGF, FGF2	-	[61]
EU/GL/TiO2	ESCs	Tissue engineering and regeneration	>0.5	Cardiomyocytes and neuron differentiation	Mef2c, Map2	Oct-04	[62]
CH-GO	SH-SY5Y	Tissue engineering and regeneration	-	neuroblast cells differentiation	-	-	[64]
rGO-PCL	ADSCs, DRG	Tissue engineering and regeneration	>1	Neuron differentiation	MBP, NGF, Akt, Tuj1	-	[66]
adECM-PDA-rGO	NSCs	Tissue engineering and regeneration	-	Neuron differentiation	Tuj1, MAP	-	[67]
rGO-Mxene	MSU-1.1, HeLa, SH-SY5Y	Tissue engineering and regeneration	>0.8	-	-	-	[68]
RGD/GO	L-929	Tissue engineering and regeneration	>1	-	-	-	[69]
SPI-SH-GA@PGO	HaCat cell	Tissue engineering and regeneration	0.6	-	Nrf2	NLRP3	[70]
rGO-Col	HUVECs, cardiomyocytes	Tissue engineering and regeneration	-	Cardiac differentiation	TrpT-2, Actn4, Cx43	-	[71]
GOG	BMSCs, HSCs, HUVECs	Tissue engineering and regeneration	-	Osteoclast, osteoblast, and angiogenic differentiation	ALP, Runx2, OCN, RANKL, VEGF	OPG	[72]
NGO/GelMa	HUVECs	Tissue engineering and regeneration	1	Angiogenic differentiation	LPAR6, YAP1	Lats1, p-YAP Ser127	[73]
GO/rGO	MSCs	Therapeutic agents	>0.8	Angiogenic and cardiac differentiation	GATA-4, ACTC1, MEF2C, GATA2, ENDOGLIN, VE-CADHERIN	-	[84]
GCE	MCF-7 cell	Therapeutic agents	Anti-proliferation	Osteogenic differentiation	-	-	[85]
PEG/GO-XN	MDA-MB-231, MDA-MB-436, MCF-10A	Cancer Therapy	Anti-proliferation	-	SNAIL, CDH2, VIM, TWIST1	CDH-1	[86]
GO	PC3 cell	Cancer therapy	>0.3	-	-	-	[87]

Table 5 Doses of Graphene Oxide Effects on Viability Cells

Doses of GO	Viability Ratio	Effect on Cell Growth	Ref.
0.1 mg/mL	> 1	Promoted cell migration	[60]
10 mg/mL	0.6	Promoted cell migration	[70]
0–400 µg/mL	1	Induced cell assembly and new blood vessel formation	[73]
10–150 µg/mL	1	Inhibit MCF-7 cell growth	[85]
10 µg/mL	1	Inhibited the migration and invasion of breast cancer cells	[86]
0–50 µg/mL	> 0.3	Promoted tumor cell proliferation	[87]

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