Tricalcium silicate cements: osteogenic and angiogenic responses of human bone marrow stem cells

Abstract

Tricalcium silicate cements (TSCs) are used in endodontic procedures to promote wound healing and hard tissue formation. The aim of this study was to evaluate and compare the effect of commonly used TSCs [mineral trioxide aggregate (MTA), Biodentine, and TotalFill] on cellular metabolism and osteogenic/angiogenic differentiation of human bone marrow mesenchymal stem cells (hBMSCs) in vitro. We tested the null hypothesis of no difference between MTA, Biodentine, and TotalFill in stem cell responses. Cells were subjected to eluates of the tested materials for up to 14 d. Cell viability was evaluated using the 3‐(4,5‐dimethyl‐thiazoyl)‐2,5‐diphenyl‐tetrazolium bromide (MTT) assay. Real‐time PCR was used to determine the levels of expression of the osteogenic factors alkaline phosphatase (ALP), osteoprotegerin (OPG), osteocalcin (OC), and collagen 1A (COL1A1), and the angiogenic factors vascular endothelial growth factor A (VEGFA) and fibroblast growth factor 1 (FGF1). ELISAs were used to measure the levels of VEGFA and ALP in culture supernatants. Mineralization in vitro of hBMSCs was assessed using Alizarin Red staining. The hBMSCs tolerated exposure to TSCs well, with Biodentine showing the most favorable effect on cell viability. Expression of ALP, COL1A1, OPG, and VEGFA were differentially affected by the materials, with Biodentine and TotalFill inducing earlier changes at gene level. Increased mineralization was observed with time, after exposure to all TSCs tested, with MTA showing the greatest effect. The results revealed different responses of hBMSCs to TSCs in vitro.

Effects of tricalcium silicate/sodium alginate/calcium sulfate hemihydrate composite cements on osteogenic performances in vitro and in vivo

“…Biologically active Ca and Si ions released from composite cements could be responsible for the beneficial effects on osteoblastic differentiation and ECM mineralization. 8,9 On the one hand, low Ca concentration (2–4 mM) is suitable for osteoblast survival and proliferation, whereas slightly higher Ca concentration (6–8 mM) favors osteoblast differentiation and sequential matrix mineralization. 23 On the other hand, appropriate Si concentration is beneficial to collagen type I formation and osteoblastic differentiation.…”

“…[4][5][6][7] The calcium and silicon ions released from C 3 S exhibit beneficial effects on osteoblast proliferation, differentiation, and extracellular matrix (ECM) mineralization. 8,9 However, the main drawbacks of C 3 S cement are the long setting time, relatively low degradation rate, and difficult handling. 10,11 On the contrary, CS cement has fast-setting property, rapid biodegradability, and desirable formability, but no bioactivity.…”

In vitro biocompatibility and bioactivity of calcium silicate‑based bioceramics in endodontics (Review)

“…Both Biodentine and MTA at high concentrations (1:2) show cytotoxicity to human BMSCs, while Biodentine at low concentrations (1:10 and 1:20) and long incubation periods exhibits an inferior ability to enhance proliferation and osteoblastic differentiation of human BMSCs compared with MTA ( 119 ). Moreover, Biodentine and MTA display an inhibitory effect on survival of human BMSCs in a concentration-dependent manner over 7 days but do not affect cell morphology ( 120 ). The cytotoxicity of Biodentine to human BMSCs may be ascribed to the calcium chloride contained in its liquid ( 121 ), which has been reported to exhibit less biocompatibility when added to MTA compared with MTA mixed with water ( 122 ).…”

“…The cytotoxicity of Biodentine to human BMSCs may be ascribed to the calcium chloride contained in its liquid ( 121 ), which has been reported to exhibit less biocompatibility when added to MTA compared with MTA mixed with water ( 122 ). Therefore, Biodentine prepared following complete setting is more compatible with human BMSCs than MTA ( 120 ). High Alp activity with mineral deposits in rat BMSCs have been found in the presence of Biodentine after 12 days ( 116 ) but the capacity of Biodentine to induce osteogenic differentiation in human BMSCs is inferior to that of MTA ( 117 , 118 ).…”

“…High Alp activity with mineral deposits in rat BMSCs have been found in the presence of Biodentine after 12 days ( 116 ) but the capacity of Biodentine to induce osteogenic differentiation in human BMSCs is inferior to that of MTA ( 117 , 118 ). MTA exhibits earlier and more pronounced calcium deposits than Biodentine ( 120 ), which may be explained by the fact that MTA produces high pH and Alp activity and promotes production of high concentration of Ca ions ( 123 ).…”