Anti‐inflammatory and immunomodulatory effects of Biodentine on human periapical lesion cells in culture

Abstract

Aim To evaluate the effect of Biodentine eluate on cytotoxicity and production of pro‐ and anti‐inflammatory cytokines and osteodestructive/osteoprotective cytokines in cultures of human periapical lesion cells. Methodology Conditioned Biodentine Medium (CBM) was prepared according to ISO 10993‐12, by incubating Biodentine in RPMI medium (0.2 g mL−1) for 3 days at 37 °C. CBM contained both released microparticles and leachable soluble components. Inflammatory cells were isolated from 22 human periapical lesions after apicectomy or tooth extraction, by collagenase/DNase digestion, and cultured in several dilutions of CBM. The composition of periapical lesion cells was determined by morphological criteria, cytotoxicity was quantified by MTT and flow cytometric apoptosis/necrosis assays, whereas the levels of produced cytokines in cell culture supernatants were measured by flow cytometry and ELISA. Student t‐test and Friedman test with Dunn's post‐test were used for comparison of parametric and nonparametric variables, respectively. Results Undiluted (100%), 75% and 50% CBM were cytotoxic for periapical lesion cells due to induction of both necrosis (100% CBM) and apoptosis (75% and 50% CBM). Noncytotoxic concentrations of CBM (25%) inhibited the production of pro‐inflammatory cytokines: TNF‐α, (P < 0.005); IL‐1β (P < 0.01); IL‐6 (P < 0.005) and chemokines IL‐8: (P < 0.005); MCP‐1 (P < 0.005), stimulated the production of anti‐inflammatory cytokine (IL‐10; P < 0.005), Th2 cytokines: IL‐4, IL‐5 and IL‐33 (all P < 0.01), and IL‐17A (P < 0.01). The concentration of CBM (12.5%) inhibited the production of IL‐6 (P < 0.05), IL‐8 (P < 0.01) and MCP‐1 (P < 0.005) and augmented the production of IL‐10 (P < 0.05). No significant effects on Th1‐related cytokines (IFN‐γ and IL‐12) and IL‐23 were detected with 25% and 12.5% CBM concentrations. Both CBM concentrations inhibited the production of osteolytic receptor activator of nuclear factor kappa‐Β ligand (RANKL), dose dependently (P < 0.005 and P < 0.01, respectively). Higher CBM concentrations decreased RANKL/osteoprotegerin (OPG) ratio (P < 0.05), without significant influence on the levels of osteoprotective OPG. Conclusion Biodentine possesses immunomodulatory properties by suppressing pro‐inflammatory and augmenting anti‐inflammatory cytokines. Together with the reduction of osteodestructive mediators, this novel root‐end filling cement could be beneficial for healing and bone reparation after the surgical treatment of periapical lesions.

The Effects of Tricalcium-Silicate-Nanoparticle-Containing Cement: In Vitro and In Vivo Studies

“…The action of RANKL can be inhibited by a natural inhibitor, OPG, which is expressed primarily on some epithelial cells, vascular endothelial cells and lymphoid cells [ 43 ]. OPG blocks RANKL/RANK interactions, thereby inhibiting osteoclast activation and bone resorption, and a decrease in the RANKL/OPG ratio was detected in a previous study [ 44 ], which is consistent with the results of this study. The results of TRAP staining, used as an osteoclast marker, also showed a decrease in TRAP-positive cells in the Biodentine group from days 7 to 28.…”

Effects of different calcium-silicate based materials on fracture resistance of immature permanent teeth with replacement root resorption and osteoclastogenesis

“…A recent study demonstrated that BD microparticles and soluble leachable components at non-cytotoxic concentrations have anti-inflammatory, immunomodulatory effects and osteoprotective properties [ 45 ]. The mechanisms responsible for these included the suppression of several cytokines and the RANKL/Osteoprotegerin (OPG) ratio decrease [ 45 ].…”

“…A recent study demonstrated that BD microparticles and soluble leachable components at non-cytotoxic concentrations have anti-inflammatory, immunomodulatory effects and osteoprotective properties [ 45 ]. The mechanisms responsible for these included the suppression of several cytokines and the RANKL/Osteoprotegerin (OPG) ratio decrease [ 45 ]. In the clastic maturation process, RANKL binds its cognate RANK receptor on the surface of monocytes and macrophages and triggers their differentiation into mature multinucleated osteoclasts with bone resorption activity [ 46 ].…”

Bioinductive and anti-inflammatory properties of Propolis and Biodentine on SHED

“…The inherent properties and micro-ingredients of test materials might be the reason behind the observed results. Biodentine possesses immunomodulatory properties by suppressing pro-inflammatory and augmenting anti-inflammatory cytokines ( Eraković et al, 2020 ), whereas CAPE, different flavonoids including artepillin C in propolis, plays a key role in its anti-inflammatory action ( Szliszka et al, 2013 ). Similarly, the anti-inflammatory properties of flavonoids are in accordance with the results obtained from Alipour M. et al, where plant flavonoids were shown their antioxidative and anti-inflammatory properties ( Alipour et al, 2021 ).…”