Bioactive molecules for regenerative pulp capping

Since the discovery of bioactive molecules sequestered in dentine, researchers have been exploring ways to harness their activities for dental regeneration. One specific area, discussed in this review, is that of dental-pulp capping. Dental-pulp caps are placed when the dental pulp is exposed due to decay or trauma in an attempt to enhance tertiary dentine deposition. Several materials are used for dental-pulp capping; however, natural biomimetic scaffolds may offer advantages over manufactured materials such as improved aesthetic, biocompatibility and success rate. The present review discusses and appraises the current evidence surrounding biomimetic dental-pulp capping, with a focus on bioactive molecules sequestered in dentine. Molecules covered most extensively in the literature include transforming growth factors (TGF-βs, specifically TGF-β1) and bone morphogenetic proteins (BMPs, specifically BMP-2 and BMP-7). Further studies would need to explore the synergistic use of multiple peptides together with the development of a tailored scaffold carrier. The roles of some of the molecules identified in dentine need to be explored before they can be considered as potential bioactive molecules in a biomimetic scaffold for dental-pulp capping. Future in vivo work needs to consider the inflammatory environment of the dental pulp in pulpal exposures and compare pulp-capping materials.

Bioactive Glass Modified Calcium Phosphate Cement with Improved Bioactive Properties: A Potential Material for Dental Pulp-Capping Approaches

Direct pulp capping (DPC) is one of the treatment plans for deep caries with mechanical pulp exposure that can replace invasive treatments. This study aimed to assess the apatite-forming ability and solubility of a calcium phosphate cement (CPC) modified with bioactive glass (BG) as a potential bioactive material for DPC.Three different biomaterials including CPC, BG, and CPC/BG composite were used in this study. For bioactivity evaluation, specimens were immersed in simulated body fluid (SBF) for 5 time periods (3, 7, 14, 21 and 28 days). The samples were analyzed by SEM, EDS and XRD to confirm the formation of hydroxyapatite. The solubility was calculated by measuring the initial and final mass according to the ISO 6876 specifications.According to the results of this study, SEM observations and XRD analysis revealed higher formation of hydroxyapatite crystals in the CPC/BG Group and also at the shorter time than those in the CPC and BG groups. Concerning solubility, the CPC group showed the most solubility after 7 days and the BG group showed the lowest one. At this time the difference between CPC and BG groups was statistically meaningful (p value=0.003). After 30 days the CPC/BG group exhibited the lowest solubility value. At the day 30, the CPC and BG groups showed significant difference in their solubility (p value=0.04).).Based on the results, addition of BG to CPC improved bioactivity properties of CPC material and did not affect its solubility adversely. The CPC/BG composite seems to be a promising material for DPC. Further in vivo studies are needed to prove its clinical success.

Human dental pulp stem cell responses to different dental pulp capping materials

Background Direct pulp capping is a vital pulp therapy for a pin-point dental pulp exposure. Applying a pulp capping material leads to the formation of a dentin bridge and protects pulp vitality. The aim of this study was to compare the effects of four dental materials, DyCal®, ProRoot® MTA, Biodentine™, and TheraCal™ LC in vitro. Methods Human dental pulp stem cells (hDPs) were isolated and characterized. Extraction medium was prepared from the different pulp capping materials. The hDP cytotoxicity, proliferation, and migration were examined. The odonto/osteogenic differentiation was determined by alkaline phosphatase, Von Kossa, and alizarin red s staining. Osteogenic marker gene expression was evaluated using real-time polymerase chain reaction. Results ProRoot® MTA and Biodentine™ generated less cytotoxicity than DyCal® and TheraCal™ LC, which were highly toxic. The hDPs proliferated when cultured with the ProRoot® MTA and Biodentine™ extraction media. The ProRoot® MTA and Biodentine™ extraction medium induced greater cell attachment and spreading. Moreover, the hDPs cultured in the ProRoot® MTA or Biodentine™ extraction medium migrated in a similar manner to those in serum-free medium, while a marked reduction in cell migration was observed in the cells cultured in DyCal® and TheraCal™ LC extraction media. Improved mineralization was detected in hDPs maintained in ProRoot® MTA or Biodentine™ extraction medium compared with those in serum-free medium. Conclusion This study demonstrates the favorable in vitro biocompatibility and bioactive properties of ProRoot® MTA and Biodentine™ on hDPs, suggesting their superior regenerative potential compared with DyCal® and TheraCal™.

Comparison of Four Dental Pulp-Capping Agents by Cone-Beam Computed Tomography and Histological Techniques—A Split-Mouth Design Ex Vivo Study

Dental pulp-capping is done to preserve vital teeth when the pulp is exposed due to caries, trauma or instrumentation. Various materials are used as pulp-capping agents. The introduction of newer materials requires scientific studies to assess their clinical efficacy. The study was designed as a split-mouth randomized analysis of four pulp-capping agents (calcium hydroxide, mineral trioxide aggregate (MTA), Biodentine and EndoSequence root repair material (ERRM)). Based on selection criteria, 15 orthodontic patients requiring the extraction of four premolars (60 teeth total) were included in the study. After pulp-capping, the teeth were extracted after 8 weeks. We analyzed the extracted teeth using cone-beam computed tomography (CBCT) and histological sections to determine the quality of the dentinal bridge and the pulpal response. Ordinal scores were given based on the completeness of the dentinal bridge, the type of bridge and the degree of pulpal inflammation. Results were analyzed using a Kruskal–Wallis test (p < 0.05) with post hoc Conover values being used when applicable. All four pulp-capping materials elicited dentinal bridge formation (60/60). MTA had the highest scores (10/15) in dentinal bridge formation followed by ERRM (8/15). Both materials showed more samples with complete dentinal bridges (9/15 each) and a favorable pulpal response (15/15). Teeth capped with calcium hydroxide showed more cases of incomplete bridge formation (9/15) and pulpal inflammation. These differences in dentinal bridge formation and pulpal inflammation were statistically significant (p 0.001 and p 0.00005, respectively), with post hoc tests revealing no significant differences between MTA and ERRM (p 0.49 and p 0.71, respectively). MTA and ERRM performed better than the other pulp-capping materials but did not differ significantly from each other. The individual preference for a pulp-capping material may be based on clinical efficacy and handling characteristics.

Evaluating the potential of an amelogenin-derived peptide in tertiary dentin formation

Several novel biomaterials have been developed for dental pulp capping by inducing tertiary dentin formation. The aim of this study was to evaluate the effect of QP5, an amelogenin-based peptide, on the mineralization of dental pulp cells (DPCs) in vitro and in vivo. The cell viability of human DPCs (hDPCs) after treatment with QP5 was determined using the Cell Counting Kit-8 (CCK-8). Migration of hDPCs was assessed using scratch assays, and the pro-mineralization effect was determined using alkaline phosphatase (ALP) staining, alizarin red staining and the expression of mineralization-related genes and proteins. The results showed that QP5 had little effect on the cell viability, and significantly enhanced the migration capability of hDPCs. QP5 promoted the formation of mineralized nodules, and upregulated the activity of ALP, the expression of mRNA and proteins of mineralization-related genes. A pulp capping model in rats was generated to investigate the biological effect of QP5. The results of micro-computed tomography and haematoxylin and eosin staining indicated that the formation of tertiary dentin in QP5-capping groups was more prominent than that in the negative control group. These results indicated the potential of QP5 as a pulp therapy agent.

Evaluation of Resin-Based Material Containing Copaiba Oleoresin (Copaifera Reticulata Ducke): Biological Effects on the Human Dental Pulp Stem Cells

The purpose of this study was to analyze in vitro the biological effects on human dental pulp stem cells triggered in response to substances leached or dissolved from two experimental cements for dental pulp capping. The experimental materials, based on extracts from Copaifera reticulata Ducke (COP), were compared to calcium hydroxide [Ca(OH)2] and mineral trioxide aggregate (MTA), materials commonly used for direct dental pulp capping in restorative dentistry. For this, human dental pulp stem cells were exposed to COP associated or not with Ca(OH)2 or MTA. Cell cytocompatibility, migration, and differentiation (mineralized nodule formation (Alizarin red assay) and gene expression (RT-qPCR) of OCN, DSPP, and HSP-27 (genes regulated in biomineralization events)) were evaluated. The results showed that the association of COP reduced the cytotoxicity of Ca(OH)2. Upregulations of the OCN, DSPP, and HSP-27 genes were observed in response to the association of COP to MTA, and the DSPP and HSP-27 genes were upregulated in the Ca(OH)2 + COP group. In up to 24 h, cell migration was significantly enhanced in the MTA + COP and Ca(OH)2 + COP groups. In conclusion, the combination of COP with the currently used materials for dental pulp capping [Ca(OH)2 and MTA] improved the cell activities related to pulp repair (i.e., cytocompatibility, differentiation, mineralization, and migration) including a protective effect against the cytotoxicity of Ca(OH)2.