# Biocompatibility and Osteo/Odontogenic Potential of Various Bioactive Root-End Filling Materials
###### Abstract  
This in vitro study aimed to investigate if different bioactive root-end filling materials can promote osteo/odontogenic differentiation of mesenchymal stem cells (MSCs) and support their viability. MSCs from porcine tooth germs were isolated. Cells were exposed to extracts from MTA Angelus, BIOfactor MTA, Medchem MTA, Well-Root ST, and Pure Portland Cement for 7 days. Viability was determined with MTS and live/dead assay. Osteo/odontogenic differentiation was evaluated with alkaline phosphatase (ALP) activity and quantitative real-time PCR (RUNX2, DMP-1, and DSPP genes) which were compared with osteo/odontogenic-induced MSCs and non-treated cells. All the tested materials supported cell proliferation and cells maintained their viability after 7 days. Osteo/odontogenic differentiation of MSCs was promoted by the tested materials in varying levels as demonstrated by increased ALP activity and upregulation of related gene markers in comparison to the control group. Pure Portland Cement demonstrated a continuous high ALP activity on day 7, showing the highest value among all materials and significantly increased in comparison to the control group (\(p<0.001\)). Significant RUNN2 expression and high ALP activity (\(p<0.001\)) similar to that of osteoogenically induced cells was detected for Pure Portland Cement after 7 days. Tested MTA-based cement materials are biocompatible and induce osteo/odontogenic differentiation in vitro. MTA materials performed similarly to Pure Portland Cement regarding osteo/odontogenic differentiation.  
d  
properties to MTA with fewer drawbacks [1]. Among MTA-based materials, ProRoot MTA was the first available MTA product, which was followed by MTA Angelus with a reduced setting time due to its decreased calcium sulfate concentration [9]. Nowadays, various MTA materials are offered in the market with different qualities regarding their setting time, color properties, or ease of handling to enhance their clinical properties. Medcem MTA (Medcem GmbH, Weinfelden, Switzerland) is a second-generation MTA that comprises Pure Portland Cement (Medcem GmbH, Weinfelden, Switzerland) with a color-stable X-ray contrast media, zirconium oxide, according to the product manual. Pure Portland Cement is similar in content except for an additional X-ray opaque ingredient, with a slightly higher hardness according to the manufacturer. Well-Root ST (Vericom, Chuncheon-si, Gangwon-Do, Republic of Korea) is a novel bioceramic root canal sealer presented in the form of a premixed injectable bioactive paste with ease of use. Recently, it was reported that Well-Root ST is an appropriate alternative to ProRoot MTA and Biodentine due to its superior angiogenesis potential as indicated by better vascularization [10]. There are still limited data available on its properties and its interactions in the scientific literature. BIOfactor MTA (Imicryl Dental, Konya, Turkey) is another bioactive material consisting of tricalcium silicate without bismuth but includes ytterbium oxide as a radiopacifier.  
The wide range of choices poses a challenge to clinicians as it is difficult to recognize the differences between these products. Hence, extensive investigations into their specific characteristics and behaviors may improve the understanding of the biological properties of these materials to give some insight to the clinician when making a valid clinical decision. To the best of our knowledge, there is no study available comparing the aforementioned bioactive MTA-based materials in terms of their biocompatibility and osteo/ odontogenic differentiation potential. Therefore, the main aim of the present study was to evaluate the cell viability and osteo/ odontogenic responses of MSCs derived from tooth germs when exposed to various MTA-based materials. Two null hypotheses were tested: (1) MTA-based materials would not interfere with the viability of stem cells and (2) all tested bioactive materials would support osteo/odontogenic differentiation of stem cells similarly.