Table 3.

Review of studies conducted on MTA, Biodentine and Cem cement

Row	Names of authors	Year	Type of calcium silicate base cement ) MTA OR Biodentin OR Cem cement)	Type of cell line used	Substance concentration	Cell exposure time	Measurement method	Results
1	Khedmat et al	2013	Biodentine (Septodont), Calcium Enriched Mixture (CEM cement, BioniqueDent), and ProRoot MTA (Dentsply Tulsa Dental).	Human monocytes were isolated from peripheral blood mononuclear cells	-	24 hr 7 day 28day	MTT assay	Biodentine and ProRoot MTA had similar biocompatibility. Biosealer and CEM cement after 48 hr of incubation were significantly more cytotoxic.
2	Omidi et al	2019	Angelus mineral trioxide aggregate (MTA; Angelus), calcium-enriched mixture (CEM; BioniqueDent), and Biodentine (Septodont)	human dental pulp stem cells (hDPSCs)	Non diluted 1:2 1:4 1:8 1:16 1:32	24 hr 48 hr 72 hr	MTT assay	The biomaterials of MTA, CEM, and Biodentine at different dilutions had no cytotoxic effects on hDPSCs at different time.
3	Saberi et al	2015	mineral trioxide aggregate (MTA), calcium-enriched mixture (CEM) cement, Biodentine (BD)	stem cells of the human apical papilla (SCAP)	1 mg of each biomaterial	24 hr 48 hr 168 hr	MTT assay	Cytotoxicity of the four materials was not significantly different from that of the control group at 24, 48 and 168 h (P>0.05).
4	Saberi et al	2016	mineral trioxide aggregate (MTA), calcium enriched mixture (CEM) cement, Biodentine (BD)	human gingival fibroblasts (HGFs)	1 mg of each biomaterial	24 hr 48 hr 168 hr	MTT assay	Cytotoxicity of MTA, CEM, Biodentine and OCP against HGFs was similar to that of the control group at 24 and 48 hours. Over time, MTA and Biodentine exhibited less cytotoxicity than other materials.
5	Küçükkaya et al	2016	MTA, calcium enriched mixture (CEM) cement, and Biodentine	human periodontal ligament fibroblasts	-	24 hr 48 hr 72 hr	WST-1 assay	There was no significant difference in cell viability amongst the test materials after each incubation period (P>0.05).
6	Zhou et al	2013	Biodentine, White Pro Root mineral trioxide aggregate (MTA)	human gingival fibroblasts	1:1 1:2 1:4 1:8	1day 3 day 7 day	flow cytometry	Cells exposed to extracts from Biodentine and MTA showed the highest viabilities at all extract concentrations. (P < .05). There was no significant difference in cell viabilities between Biodentine and MTA during the entire experimental period (P>0.05).
7	Youssef et al	2019	mineral trioxide aggregate (MTA), Biodentine	dental pulp stem cells (DPSCs)	0.5 mg/ml	3 day	MTT assay	All capping materials showed variable cytotoxicity against DPSCs (77% for Emdogain, 53% for MTA, 26% for Biodentine and 16% for Ca(OH)2 compared to control (P value < 0.0001). Our results suggest MTA, Biodentine and Emdogain exhibit similar attributes and may score better than Ca(OH)2.
8	Weekate et al	2021	Biodentine, ProRoot MTA	lipopolysaccharide (LPS)-induced human dental pulp cells (hDPCs)	-	24 hr 48 hr	Alamar blue assay	Both Biodentine and MTA extracts promoted cell survival, whereas the combination of NAC to these material extracts significantly increased the number of viable cells at 24 h (P<0.05).
9	Tomas-Catala et al	2018	MTA Repair HP, NeoMTA Plus, and Biodentine	human dental pulp stem cells (hDPSCs)	Non diluted 1:2 1:4	24 hr 48 hr 72 hr	MTT assay	Cell viability was moderate after 24 and 48 hours in the presence of MTA Repair HP and NeoMTA Plus, whereas at 48 and 72 hours, Biodentine showed higher rates of cell viability than MTA Repair HP and NeoMTA Plus (P<0.001). The new pulp-capping materials MTA Repair HP, NeoMTA Plus, and Biodentine showed a suitable degree of cytocompatibility with hDPSCs.
10	Sultana et al	2018	ProRoot MTA (MTA; Dentsply Tulsa Dental, Tulsa, OK), Biodentine (BD; Septodont, Saint Maur de Fosses, France)	human bone marrow derived mesenchymal stem cells (hBMSCs)	formulated into discs	1day 3 day 5 day 7 day	MTT assay	MTA have shown the best biocompatibility among the tricalcium silicate materials used with no significant difference between them
11	Sismanoglu, S. Ercal, P.	2022	Biodentine, NeoMTA Plus	tooth germ-derived stem cells (TGSCs)	-	7 day	MTS cell proliferation assay	TGSCs remained viable after 7 days of incubation with all tested materials.
12	Samyuktha et al	2014	mineral trioxide aggregate (MTA), and Biodentine	human periodontal ligament fibroblasts	-	48 hr 72 hr	trypan blue dye assay+inverted phase contrast microscope	Mineral trioxide aggregate was shown to be less toxic to periodontal ligament fibroblasts than Endosequence Root Repair Material and Biodentine. After 24-hour time period, MTA, Endosequence, Biodentine, and control group resulted in cell viabilities of 94.26%, 86.19%, 85.97%, and 96.17%. After 48-hour time period, Endosequence, MTA, Biodentine, and control group resulted in cell viabilities of 82.94%, 82.31%, 81.81%, and 93.34%. Table 2 showed that all the test materials showed no statistical significant difference between them (P>0.05).
13	Akbulut et al	2018	Biodentine, Micro-Mega mineral trioxide aggregate (MM-MTA)	human periodontal ligament (hPDL) fibroblasts	1:1 1:2 1:4 1:8	24 hr	XTT assay	Three-day samples were more cytotoxic than 1-day samples (P<0.05). Eluates from the cements at 1:1 dilution were significantly more cytotoxic (P<0.05). This in vitro study demonstrated that Biodentine and Compomer were more biocompatible than the other root-end filling materials
14	Pinheiro et al	2018	mineral trioxide aggregate (MTA; Angelus, Londrina, PR, Brazil) and Biodentine (BD; Septodont, Saint-Maur-de-Fosses, France)	Fibroblasts (3T3)	-	-	MTT assay and sulforhodamine B assays	NeoMTA Plus showed a biocompatible behavior similar to mineral trioxide aggregate and Biodentine. The material extracts induced greater viability on fibroblast cells after setting.
15	Pelepenko et al	2021	ProRoot MTA and Biodentine	human fibroblast cells	-	-	MTT assay	White-MTAFlow showed MTT cytocompatibility similarly to the control group. White-MTAFlow in ‘thin’ consistency presents comparable physicochemical, biological, and antimicrobial properties to ProRoot MTA and Biodentine, and does not cause color alteration in dentin.
16	Pedrosa et al	2022	Biodentine and MTA Repair HP	human dental pulp cells (hDPCs)	1:1, 1:4, and 1:16	24 hr 48 hr 72 hr	MTT assay	Cell viability of LPS-activated hPDCs was higher than untreated control in 48 and 72 h (P<0.05).
17	Pedrosa et al	2022	Biodentine, MTA Repair HP and White MTA	human periodontal ligament stem cells (hPDLSCs)	pure, 1:4 and 1:16	24 hr 48 hr 72 hr	MTT assay	At 24 h, pure extract of MTA Repair HP and Biodentine 1:16 presented higher cell viability compared to control. Lower cell viability was found for pure extract of Cimmo HD, MTA Repair HP 1:4 and 1:16, and White MTA 1:16. At 48 h, pure extract of Bio-C Repair and MTA Repair HP presented higher cell viability compared to control. At 72 h, only the pure extract of MTA Repair HP led to higher cell proliferation compared to control.
18	Pedano et al	2018	Nex-Cem MTA (GC), Biodentine (Septodont)	Human dental pulp cells	(100%, 50%, 25% and 10%)	-	XTT-colorimetric assay	all three cements stimulated proliferation, migration and odontogenic differentiation of HDPCs.
19	Margunato et al	2015	ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), Biodentine (Septodont, Saint Maur des Fossés, France), and MM-MTA (Micro-Mega, Besançon Cedex, France)	human bone marrow stem cells (hBMSCs)	-	days 1, 3, 7, and 14	3-(4,5-dimethyl-thiazol-2-yl)-5-(3-carboxy-methoxy-phenyl)-2-(4-sulfo-phenyl)-2H tetrazolium assay	MTA, Biodentine, and MM-MTA did not exhibit a cytotoxic effect on hBMSCs after 14 days in culture.
20	Donghee et al	2020	ProRoot MTA (Dentsply Tulsa Dental Specialties), Biodentine (Septodont), and RetroMTA (BioMTA)	human gingiva-derived stem cells (GDSCs)	-	-	MTT assay	In the MTT assay, no significant differences were found among the ProRoot MTA, Biodentine, and control groups during the test period (p > 0.05). The Endocem Zr and RetroMTA groups showed relatively lower cell viability than the control group at day 7 (p < 0.05).
21	Jovanovic et al	2014	MTA and Biodentine	permanent fibroblast cell lines (MRC-5 and L929)	-	24 hr 48 hr	MTT assay	MTT test showed that after 24 and 48 hours in both cell cultures, Biodentine had the largest percentage of citotoxicity. The lowest percentage of cytotoxicity showed MTA in both groups.
22	Hengameh, et al	2014	CEM cemen and MTA	human mesenchymal stem cells (hMSCs)	-	-	MTT assay	Cell viability was not significantly different. CEM cement has acceptable toxicity.
23	Gomes-Cornelio et al	2017	Biodentine (BIO, Septodont), MTA Plus (MTA P, Avalon)	human osteoblastic cells (Saos-2)	-	-	MTT assay	Results All tested cements showed dose-dependent responses in cell viability (MTT). All materials had suitable biocompatibility and bioactivity. The MTA P, BIO and CSCR ZrO2 groups had the highest viability rates.
24	Assadian et al	2022	OrthoMTA (OMTA), Biodentine (BD) and Calcium-Enriched Mixture (CEM)	human dental pulp stem cells (hDPSCs)	10, 25, 50 and 100%	Days 1, 3 and 5	-	Optimal cell proliferation was observed in all groups, regardless of concentration and time-point.
25	Dahake et al	2020	MTA (Mineral Trioxide Aggregate) and Biodentine	Stem Cells from Human Exfoliated Deciduous teeth (SHED)	-	7 day	MTT assay	It was observed that EMD imparted the highest cell viability at the end of 7 days (p < 0.001) followed by Biodentine and MTA.
26	Costa et al	2016	ProRoot MTA (Dentsply Tulsa Dental, Tulsa, OK), MTA Plus (Prevest Denpro Limited, Jammu City, India), MTA Fillapex (Angelus, Londrina, PR, Brazil), and Biodentine (Septodont, Saint-Maur-des-Fosses, France)	human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs)	(1:2-1:20)	-	-	Diluted extracts from MTA ProRoot and MTA Plus had evident stimulatory effects on the proliferation of hMSCs. MTA Fillapex exhibited the highest toxicity in hMSCs and HUVECs.
27	Collado-Gonzalez et al	2017	Biodentine (Septodont, Saint-Maur-des-Fosses, France) MTA (Angelus, Londrina, PR, Brazil)	stem cells isolated from human exfoliated primary teeth (SHEDs)	-	24, 48 and 72h	MTT assay	Biodentine exhibited better cytocompatibility and bioactivity than MTA Angelus, Theracal LC and IRM.
28	Bossù, M. Mancini, P.	2021	ProRoot MTA and Biodentine	Human osteogenic sarcoma (Saos-2) cells	-	-	-	Cell viability assay demonstrated that Saos-2 cells had a dose- and time-dependent cytotoxicity to both analyzed cements, although cells exposed to ProRoot MTA showed a better cell vitality than those exposed to Biodentine (p < 0.001).
29	Bortoluzzi et al	2015	MTA Angelus and Biodentine	human dental pulp stem cells (hDPSCs)	-	-	XTT assay and flow cytometry	The cytotoxic effects of Biodentine and TheraCal LC on hDPSCs were time- and concentration-dependent.
30	Birant et al	2021	NeoMTA Plus, ProRootMTA and Biodentine	Dental pulp stem cells (DPSCs)	-	Days 1, 3 and 7	flow cytometry using an Annexin V detection kit	All groups showed cell viability similar to that of the control group on 1st, 3rd and 7th d. Although Biodentine exhibited higher cell viability rates than the other material groups, no statistically significant differences were noted between the sampled days (p > 0.05). All materials extracts are not cytotoxic.
31	Attik et al	2014	Biodentine(TM) and White ProRoot(R) mineral trioxide aggregate (MTA(R))	MG63 osteoblast-like cells	-	Days 1, 3 and 5	MTT assay	The MTT test for Biodentine(TM) was similar to that of MTA(R).
32	Agrafioti et al	2016	Biodentine and MTA	dental pulp stem cells (DPSCs)	-	4 day 7 day	MTT assay	Biodentine expressed significantly higher cell viability compared with all other groups after 4 days, with no differences after 7 days. Notably, cell viability was significantly greater in 24-hour set MTA compared with 1-hour set MTA and control groups after 7 days.