Effects of Intracanal Antimicrobials on Viability and Differentiation of Stem Cells From the Apical Papilla: An In Vitro Study.

BACKGROUND: Recent studies have indicated that intracanal antimicrobials used to disinfect the root canal in regenerative endodontic therapies (RETs) may be cytotoxic to stem cells from the apical papilla (SCAP), leading to inconsistent treatment outcomes. However, the effects of intracanal antimicrobial agents on the odontogenic differentiation capacity of SCAP at sub-lethal concentrations have not been investigated. The aim of this study was to determine the effects of intracanal antimicrobials on SCAP viability and odontogenic differentiation capacity using a clinically relevant concentration range (0.1-0.8 mg/mL). METHODS: Immature human third molars were collected from 71 patients and the apical papillae were harvested to form single-cell suspensions. The cytotoxic effects of intracanal antimicrobials including double antibiotic paste (DAP), triple or modified-triple antibiotic paste (TAP or MTAP), and calcium hydroxide (Ca(OH)2) on STRO-1+ SCAP were assessed using AlamarBlue and Live/Dead assays after exposing cells to treatment groups for 7 days at 0.1 to 0.8 mg/mL. The odontogenic differentiation potential of STRO-1+ SCAP was evaluated by immunocytochemistry staining of dentin matrix protein-1 and dentin sialophosphoprotein expression. RESULTS: All concentrations of TAP significantly reduced STRO-1+ SCAP viability and odontogenic differentiation (P < .001), whereas no DAP concentrations were significantly cytotoxic. Ca(OH)2 and MTAP concentrations below 0.4 mg/mL and 0.2 mg/mL, respectively, did not significantly reduce viability. The DAP, MTAP, and Ca(OH)2 did not significantly impact the odontogenic differentiation capacity of STRO-1+ SCAP. CONCLUSION: The varying effects of intracanal antimicrobials on STRO-1+ SCAP in vitro suggest amendments to the current root canal disinfection protocol may improve the success of RETs.

Biomaterials and Scaffold Design Strategies for Regenerative Endodontic Therapy.

Challenges with traditional endodontic treatment for immature permanent teeth exhibiting pulp necrosis have prompted interest in tissue engineering approaches to regenerate the pulp-dentin complex and allow root development to continue. These procedures are known as regenerative endodontic therapies. A fundamental component of the regenerative endodontic process is the presence of a scaffold for stem cells from the apical papilla to adhere to, multiply and differentiate. The aim of this review is to provide an overview of the biomaterial scaffolds that have been investigated to support stem cells from the apical papilla in regenerative endodontic therapy and to identify potential biomaterials for future research. An electronic search was conducted using Pubmed and Novanet databases for published studies on biomaterial scaffolds for regenerative endodontic therapies, as well as promising biomaterial candidates for future research. Using keywords "regenerative endodontics," "scaffold," "stem cells" and "apical papilla," 203 articles were identified after duplicate articles were removed. A second search using "dental pulp stem cells" instead of "apical papilla" yielded 244 articles. Inclusion criteria included the use of stem cells from the apical papilla or dental pulp stem cells in combination with a biomaterial scaffold; articles using other dental stem cells or no scaffolds were excluded. The investigated scaffolds were organized in host-derived, naturally-derived and synthetic material categories. It was found that the biomaterial scaffolds investigated to date possess both desirable characteristics and issues that limit their clinical applications. Future research investigating the scaffolds presented in this article may, ultimately, point to a protocol for a consistent, clinically-successful regenerative endodontic therapy.