In Vitro Response of Dental Pulp Stem Cells to Calcium Silicate-Based Cements: A Systematic Review and Meta-Analysis of Preclinical Evidence.

Abstract

Regenerative endodontics utilizes stem cell biology and bioactive materials to restore pulp vitality. Human dental pulp stem cells (hDPSCs), with their self-renewal and odontogenic differentiation potential, are central to regenerative endodontics. Hydraulic calcium silicate-based cements (HCSCs), such as mineral trioxide aggregate (MTA) and Biodentine (Septodont, Saint-Maur-des-Fossés, France), are widely used in vital pulp therapies to promote pulp vitality recovery. This research evaluates the response of hDPSCs to HCSCs through a meta-analysis that assesses their cytocompatibility and bioactive effects on hDPSCs in laboratory conditions. The review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered at PROSPERO (CRD42023473456). A complete search of PubMed, Scopus, and Web of Science databases included all scientific articles between 2014 and 2023. Research involving hDPSCs exposed to HCSCs included in vitro investigations that studied both cell survival and proliferation, as well as migration, adhesion, and odontogenic differentiation. The risk assessment for potential bias in the studies used the Cochrane ROB-2 tool. The monitoring process for assessing the effects of pooled cell viability relied on RevMan 5.3 software (The Cochrane Collaboration, London, UK) for the execution of this meta-analysis. Quality synthesis included 16 studies, while the meta-analysis included three studies. The majority of research findings demonstrate that MTA, when combined with Biodentine, particularly at concentrations of 0.2-2 mg/mL, along with accelerated MTA and a calcium-enriched mixture (CEM, BioniqueDent, Tehran, Iran), effectively boosted hDPSC cell viability and migration, while also promoting their odontogenic differentiation. The laboratory tests demonstrated that TheraCal LC (BISCO, Inc., Schaumburg, IL, USA) produced toxic effects, but TheraCal PT exhibited non-toxic properties. Based on meta-analyzed data, the control groups attained a standardized mean difference of -0.26 (95% CI: -0.90 to 0.38), though this difference proved non-significant at p > 0.05. The examination of funnel plots found no indication of important publication bias. The vital pulp treatment success of MTA, Biodentine, accelerated MTA, and CEM as hydraulic calcium silicate-based biomaterials becomes more evident due to their induction of positive hDPSC biological outcomes, such as enhanced cell viability and migration and enhanced odontogenic differentiation potential. In addition, in vivo research, along with clinical trials, must precede material selection optimization for implementing regenerative endodontic treatments.