Comparative Biocompatibility and Odonto-/Osteogenesis Effects of Hydraulic Calcium Silicate-Based Cements in Simulated Direct and Indirect Approaches for Regenerative Endodontic Treatments: A Systematic Review

Background: Regenerative dentistry is the operation of restoring dental, oral and maxillofacial tissues. Currently, there are no guidelines for the ideal cement/material in regenerative endodontic treatments (RET). Hydraulic calcium silicate-based cements (hCSCs) are currently the material of choice for RET. Objectives: This systematic review was conducted to gather all of the different direct and indirect approaches of using hCSCs in RET in vitro and in vivo, and to ascertain if there are any superiorities to indirect approaches. Methods and Materials: This systematic review was conducted according to the 2020 PRISMA guidelines. The study question according to the PICO format was as follows: Comparison of the biological behavior (O) of stem cells (P) exposed to hCSCs through direct and indirect methods (I) with untreated stem cells (C). An electronic search was executed in Scopus, Google Scholar, and PubMed. Results: A total of 78 studies were included. Studies were published between 2010 and 2022. Twenty-eight commercially available and eighteen modified hCSCs were used. Seven exposure methods (four direct and three indirect contacts) were assessed. ProRoot MTA and Biodentine were the most used hCSCs and had the most desirable results. hCSCs were either freshly mixed or set before application. Most studies allowed hCSCs to set in incubation for 24 h before application, which resulted in the most desirable biological outcomes. Freshly mixed hCSCs had the worst outcomes. Indirect methods had significantly better viability/proliferation and odonto-/osteogenesis outcomes. Conclusion: Biodentine and ProRoot MTA used in indirect exposure methods result in desirable biological outcomes.