You are currently viewing a new version of our website. To view the old version click .
MDPIMDPI
Search all articles
Materials
Download PDF
  • Feature Paper
  • Review
  • Open Access

27 March 2019

Bioactivity of Bioceramic Materials Used in the Dentin-Pulp Complex Therapy: A Systematic Review

,
,
,
and
1
Department of Stomatology, Universitat de València, 46010 Valencia, Spain
2
Cellular Therapy and Hematopoietic Transplant Unit, Hematology Department, Virgen de la Arrixaca Clinical University Hospital, IMIB, University of Murcia, 30120 Murcia, Spain
3
School of Dentistry, Faculty of Medicine, University of Murcia, 30100 Murcia, Spain
4
Department of Dentistry, Faculty of Health Sciences, Universidad CEU-Cardenal Herrera, 46115 Alfara del Patriarca (Valencia), Spain
Materials2019, 12(7), 1015;https://doi.org/10.3390/ma12071015
This article belongs to the Special Issue Biomaterials for Dental Healing
Version Notes
Order Reprints

Abstract

Dentistry-applied bioceramic materials are ceramic materials that are categorized as bioinert, bioactive and biodegradable. They share a common characteristic of being specifically designed to fulfil their function; they are able to act as root canal sealers, cements, root repair or filling materials. Bioactivity is only attributed to those materials which are capable of inducing a desired tissue response from the host. The aim of this study is to present a systematic review of available literature investigating bioactivity of dentistry-applied bioceramic materials towards dental pulp stem cells, including a bibliometric analysis of such a group of studies and a presentation of the parameters used to assess bioactivity, materials studied and a summary of results. The research question, based on the PICO model, aimed to assess the current knowledge on dentistry-based bioceramic materials by exploring to what extent they express bioactive properties in in vitro assays and animal studies when exposed to dental pulp stem cells, as opposed to a control or compared to different bioceramic material compositions, for their use in the dentin-pulp complex therapy. A systematic search of the literature was performed in six databases, followed by article selection, data extraction, and quality assessment. Studies assessing bioactivity of one or more bioceramic materials (both commercially available or novel/experimental) towards dental pulp stem cells (DPSCs) were included in our review. A total of 37 articles were included in our qualitative review. Quantification of osteogenic, odontogenic and angiogenic markers using reverse transcriptase polymerase chain reaction (RT-PCR) is the prevailing method used to evaluate bioceramic material bioactivity towards DPSCs in the current investigative state, followed by alkaline phosphatase (ALP) enzyme activity assays and Alizarin Red Staining (ARS) to assess mineralization potential. Mineral trioxide aggregate and Biodentine are the prevalent reference materials used to compare with newly introduced bioceramic materials. Available literature compares a wide range of bioceramic materials for bioactivity, consisting mostly of in vitro assays. The desirability of this property added to the rapid introduction of new material compositions makes this subject a clear candidate for future research.

1. Introduction

Within the field of biomedical therapeutics, we can highlight the concept of tissue engineering to refer to the development of procedures and biomaterials that aim to devise new tissues to replace those damaged, following the principles of cellular and molecular biology and taking as a premise the search for “biological solutions for biological problems” [1].
In 2007, the American Association of Endodontists adopted the term “regenerative endodontics” to refer to the concept of tissue engineering applied to the restoration of root canal health, in a way that continuous development of the root and tissues surrounding it is promoted [2].
The introduction of the so-called bioceramic materials meant a great advance for this new paradigm in endodontic therapy [3], given their biocompatible nature and excellent physicochemical properties [4]. Categorized as bioinert, bioactive and biodegradable [5], dentistry-applied bioceramic materials are ceramic materials which share a common characteristic of being specifically designed to fulfil their function; they are able to act as root canal sealers, cements, root repair or filling materials [4]. Applied to vital pulp therapy, bioceramic materials can be used in cases of pulp exposition from trauma, caries or other mechanical causes, as direct pulp cappers [6].
Properties like biocompatibility and bioactivity are to be expected in dentistry-applied bioceramic materials for their use in vital pulp therapy [7]. The first one refers to the “ability to perform as a substrate that will support the appropriate cellular activity, including the facilitation of molecular and mechanical signaling systems, in order to optimize tissue regeneration, without eliciting any undesirable local or systemic responses in the eventual host” [8], while bioactivity goes even further, and is only attributed to those materials which are capable of inducing a desired tissue response from the host [9] by the use of biomimetic approaches [10]. The term differs depending on the field in which it is implemented, being related to the cellular effects induced by biologically active ions and substances released from biomaterials in the field of tissue engineering, but referred to as the biomaterial’s capability of forming hydroxyl apatite mineral on its surface both in vitro and in vivo in the field of biomaterial science [11].
Considering these desirable characteristics of bioceramic materials, it seems convenient to analyze the interaction between human dental pulp stem cells (hDPSCs), which are post-natal stem cells with mesenchymal stem cell (MSCs)-like characteristics, like auto-renewal ability and multilineage differentiation potential [12], and them; as their combined use could mean and advancement in the field of regenerative endodontics.
Cytotoxicity and biocompatibility of a wide range of bioceramic materials towards dental stem cells (DSCs) have been investigated in numerous studies [13,14,15,16,17]; among others. The well-known Pro-Root MTA (Dentsply Tulsa Dental Specialties, Tulsa, OK, USA) has been shown to increase osteoblast, fibroblast, cementoblast, odontoblast and pulp cell differentiation, but its handling difficulty among other limitations encourages for a search for alternative materials [13]. Materials like Biodentine (Septodont, Saint Maurdes-Fosses, France) and TheraCal LC (Bisco Inc., Schaumburg, IL, USA) are examples of bioceramic materials introduced posteriorly in dentistry for their use in vital pulp therapy as blood clot protectors in pulpal revascularization procedures, standing out for their consistency, easier manipulation and tricalcium silicate composition [16].
However, to the best of the authors’ knowledge, there has been no effort to sort and summarize studies analyzing bioactivity of such materials into more homogenous subgroups that would allow for an easier analysis of the evidence.
The aim of this study is to present a systematic review of available literature investigating bioactivity of dentistry-applied bioceramic materials towards dental pulp stem cells; including a bibliometric analysis of such group of studies and a presentation of the parameters used to assess bioactivity, materials studied and summary of results.

2. Materials and Methods

This systematic review was conducted in accordance with the PRISMA guidelines or preferred reporting items for systematic reviews and meta-analyses [18]. Our review was not eligible for registration with PROSPERO, as it did not involve health studies in which participants were people nor animal research studies exclusively.
In terms of the research question, based on the PICO model, our review aimed to assess the current knowledge on dentistry-based bioceramic materials by exploring to what extent they express bioactive properties in in vitro assays and animal studies when exposed to dental pulp stem cells, as opposed to a control or compared to different bioceramic material compositions, for their use in the dentin-pulp complex therapy.

2.1. Inclusion and Exclusion Criteria

Studies assessing bioactivity of one or more bioceramic materials (both commercially available or novel/experimental) towards DPSCs were included in our review. We established bioactivity assessment as any test or measurement for odontogenic, osteogenic, angiogenic and/or mineralization potential of DPSCs exposed both directly or indirectly to bioceramic materials. Studies assessing cytotoxicity and/or biocompatibility alone i.e., cell viability or proliferation were excluded. Studies assessing any other type of stem cell apart from DPSCs were also excluded.
The series of inclusion and exclusion criteria were established by a consensus reached from all authors after discussion, considering the research question and the objectives of the study while aiming for an ample range of results to be provided from the search.

2.2. Search Strategy

2.2.1. Sources of Information

To identify potentially relevant studies, a thorough electronic search was made in PubMed, Web of Science, Scopus, Embase, Cochrane, and Lilacs databases. Study search was performed during October, November and December 2018. In particular cases, the authors of the articles were contacted by email to request missing information. The structured search strategy and data extraction were conducted by an individual examiner.

2.2.2. Search Terms

The search strategy included 6 Mesh (Medical Subject Heading) terms: “Silicate”, “Calcium Silicate”, “Calcium phosphate”, “Calcium aluminosilicate”, “Hydroxyapatite” and “Gene Expression”; and 13 uncontrolled descriptors: “Bioceramic”, “Bioceramics”, “Bioactivity”, “Bioactive”, “Mineralisation”, “Mineralization”, “Differentiation”, “Proliferation”, “Odontogenic”, “Osteogenic”, “Dentinogenic”, “Cementogenic” and “Dental Stem Cells”. Boolean operators (“OR” and “AND”) were used to join search terms related to the search question (Figure 1).
Figure 1. Search strategy illustration.

2.2.3. Study Selection

Articles identified using the search terms were exported to RefWorks (ProQuest, MI, USA) to check for duplicates. Once duplicates were discarded, a first screening of record titles and abstracts was carried out according to the previously described inclusion and exclusion criteria. Remaining studies were assessed for eligibility and qualitative synthesis by full-text screening.

2.2.4. Study Data

For the bibliometric analysis, the following variables were recorded for each article: author and year of publication, journal, country, and institution. For the synthesis of study methodology, a summary of the materials and methods of included studies was transcribed by listing the following variables: study type, bioceramic materials used, bioactivity analysis and duration of the analysis. For the synthesis of results, studies were categorized in terms of the significant results found, the duration in which these significant results were found, and their significance level.

2.3. Quality Assessment

The quality of the studies was assessed using a modified CONSORT checklist of items for reporting in vitro studies of dental materials [19] and the ARRIVE guidelines for reporting animal research [20].

3. Results

3.1. Study Selection and Flow Diagram

The search identified 1023 preliminary references related to the bioactivity of bioceramic materials towards dental stem cells, of which 355 were found in PubMed, 473 in Web of Science, 179 in Embase, 15 in Scopus, and 1 in Cochrane databases. Search made in LILACS produced no results. After excluding 203 duplicates, the remaining 820 were screened. Of these, 783 were excluded on reading the title and abstract as they did not fulfil our inclusion criteria. The resulting 37 articles were examined at full-text level, and all of them resulted to be eligible for our review (Figure 2).
Figure 2. Systematic flow-chart representing study inclusion.

3.2. Study Characteristics

3.2.1. Bibliometric Analysis

All corresponding authors of the included studies were associated with an academic institution or university. The distribution of included studies by year of publication, country, and journal is presented in Figure 3.
Figure 3. Bibliometric Analysis: distribution of included studies by year of publication (A), country (B) and journal (C). Studies included in the category “other” only appear once for the given bibliometric parameter.

3.2.2. Bioactivity Analysis

A wide range of analyses of bioactivity were presented from the included studies. The most common analysis was the quantification of the expression of odontogenic, osteogenic and/or angiogenic markers or genes using reverse transcription polymerase reaction (RT-PCR), followed by alkaline phosphatase (ALP) enzyme activity assays and Alizarin Red Staining (ARS) to assess mineralization potential.
Other analyses include western blot, micro-computed tomography (micro-CT), scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared (ATR-FTIR), transmission electron microscopy (TEM), histological analysis, immuno-fluorescence, and immuno-histochemical assays. Bioactivity analyses alongside with their duration and a description of the study associated with them are presented in Table 1.
Table 1. Summary of the methodology of included studies.

3.2.3. Study Type

Articles included fell into two main categories in terms of type of study: in vitro, or animal study. In some cases, articles presented both an in vitro and an animal study [26,27,37]. There were two studies which analyzed bioactivity of bioceramic materials towards hDPSCs ex vivo [33,42].

3.2.4. Cell Variant

All studies included used dental pulp stem cells (DPSCs) as their cell variant to assess bioceramic material bioactivity.

3.2.5. Bioceramic Materials Used

Bioceramic materials studied ranged from commercially available (Table 2) to novel or experimental materials (Table 3). A separate category was presented for bioceramic materials which were combined with an additive for their analysis (Table 4).
Table 2. List of commercially available bioceramic materials studied.
Table 3. List of experimental/novel bioceramic materials studied.
Table 4. List of bioceramic materials and additives studied.

3.3. Quality Assessment

All in vitro studies analyzed using the modified CONSORT checklist [19] (Table 5) presented a structured abstract (item 1) and an introduction which provided information about the background of the bioceramic material and/or bioactivity analysis studied (item 2a). Within the introduction, the majority of studies presented clear objectives and hypotheses (item 2b). Description of methodology as well as of the variables studied was sufficiently clear to allow for replication in all studies (items 3 and 4), but none of them presented a detailed report of the calculation of sample size or random allocation sequence (items 5–9). All studies indicated the statistical method used (item 10), but presented significance level as p values, and not confidence intervals (item 11). Discussions generally included a brief synopsis of the key findings and comparisons with relevant findings from other published studies, but often failed to address the limitations of the studies, which we considered as a reason for non-fulfillment (item 12). Sources of funding (if any) were indicated in the majority of studies (item 13), and indications for access to full trial protocols were obviated in all studies (item 14).
Table 5. Results of the assessment of in vitro studies by the use of the modified CONSORT checklist [19]. Cells marked with an asterisk “*” represent study fulfilment for the given quality assessment parameter. Cells left blank represent non-fulfilment.
Only three out of the five animal studies analyzed using the ARRIVE guidelines [20] (Table 6) were headed with a sufficiently descriptive title (item 1), but all of them provided a detailed abstract (item 2). All studies provided sufficient scientific background (item 3a) and established clear objectives (item 4) in the introduction, but failed to justify the use of the animal species studied to address the scientific objectives (item 3b). Ethical statements were clear in all studies (item 5), and study design, experimental procedures were detailed enough in all except one (items 6 and 7). Details about the experimental animals and how they were distributed in the study design were included in every study (items 8–11 and 14), but housing and husbandry information was obviated in all cases (item 9). Both experimental outcomes and statistical methods were described in all studies (items 12 and 13). All studies reported the results for each analysis carried out with a measure of precision (item 15), but all of them failed to report baseline data about health status of the animals studied and any adverse effects they could have suffered after the experiment (items 14 and 17). Lastly, items referring to the discussion were fulfilled by all studies (items 18–20).
Table 6. Results of the assessment of animal studies by the use of the ARRIVE guidelines [20].

3.4. Study Tesults

Significant results from included in vitro studies are presented in Table 7, Table 8, Table 9, Table 10, Table 11, Table 12, Table 13, Table 14, Table 15, Table 16 and Table 17, and significant results from included animal research studies are presented in Table 18.
Table 7. Summary of the results of included studies showing significant differences between various bioceramic materials or different concentrations of the same bioceramic material for osteogenic, odontogenic and/or angiogenic gene expression.
Table 8. Summary of the results of included studies showing significant differences between a bioceramic material with an additive and the bioceramic material itself for osteogenic, odontogenic and/or angiogenic gene expression.
Table 9. Summary of the results of included studies showing significant differences between a bioceramic material and a control for osteogenic, odontogenic and/or angiogenic gene expression.
Table 10. Summary of the results of included studies showing significant differences between a bioceramic material and a non-bioceramic material for osteogenic, odontogenic and/or angiogenic gene expression.
Table 11. Summary of the results of included studies showing significant differences between various bioceramic materials or different concentrations of the same bioceramic material for ARS staining.
Table 12. Summary of the results of included studies showing significant differences between a bioceramic material with an additive and the bioceramic material itself for ARS staining.
Table 13. Summary of the results of included studies showing significant differences between a bioceramic material and a control for ARS staining.
Table 14. Summary of the results of included studies showing significant differences between various bioceramic materials or different concentrations of the same bioceramic material for ALP activity.
Table 15. Summary of the results of included studies showing significant differences between a bioceramic material with an additive and the bioceramic material itself for ALP activity.
Table 16. Summary of the results of included studies showing significant differences between a bioceramic material and a control for ALP activity.
Table 17. Summary of the results of included studies showing significant differences for another bioactivity-related analysis.
Table 18. Summary of the significant results of included studies categorized as animal studies.

3.4.1. Results for RT-PCR Analysis

Results for bioactivity-related marker expression using RT-PCR comparing a bioceramic material with mineral trioxide aggregate (Nex MTA/PR-MTA/MTA) showed positive significant results for the studied bioceramic materials (Exp. PPL and BD, [22]; Nano-HA, [21]), or mixed results depending on the gene/marker studied (Quick-Set2, [31]) or the concentration of material used (iRoot BP, (56]) [Table 7).
All studies comparing a bioceramic material and an additive with the bioceramic material itself showed positive significant results for the bioceramic material in combination with the additive (GNP-CPC, [25]; SC + LLLI, [30]; CPC-BGN, [32]; hTDM/SC, [33]; MTA-CaCl2 and MTA-Na2HPO4, [46]), except for one case (MTA+UW/PG, [35]) in which the bioceramic material itself produced better results (Table 8).
The majority of studies comparing a bioceramic material and a control showed positive significant results for the bioceramic material (Gel-HA-TCP, [23]; Zn0/1/2/3, [28]; Quick-set2 and PR-MTA, [31]; MTA and BD, [34]; BD, [38]; MTA, [40]; MTA, [43]; MTA, [44]; MTA and Theracal, [49]; MTA and BD, [50]; CaSi-αTCP, [51]; CSP, [54]; Ca3SiO5, [57]), and the rest showed mixed results depending on de gene/marker studied (Exp. PPL, BD and Nex-MTA, [22]; HA-CPC, [26]; SC, [33]; CaP, [41]; FS and BD, [48]) (Table 9).
Studies comparing a bioceramic material and a non-bioceramic material did not show positive significant results for the bioceramic materials studied. One of the studies showed that DDM produced a greater bioactivity-related gene expression than HA-CPC [26]; and the other one showed mixed results for Ca3SiO3, which produced a greater expression of some markers but not others compared to Ca(OH)2 [57] (Table 10).

3.4.2. Results for ARS Staining

Results for ARS staining comparing a bioceramic material with mineral trioxide aggregate (MTA, PR-MTA) showed negative significant results for the studied bioceramic materials (Quick-Set2, [31]; Theracal, [49]) (Table 11).
Both studies comparing a bioceramic material and an additive with the bioceramic material itself showed positive significant results for the bioceramic material in combination with the additive (γION-CPC and αION-CPC, [24]; GNP-CPC, [25]) (Table 12).
All studies comparing a bioceramic material and a control showed positive significant results for the bioceramic materials studied (Gel-HA-TCP, [23]; Zn0/1/2/3, [28]; PR-MTA and Quick-Set2, [31]; BD, Theracal and MTA, [34]; BD, [38]; MTA, [40]; CaP, [41]; FS0.2, [48]; PR-MTA and Theracal, [49]; Ca3SiO5, [57]) (Table 13).

3.4.3. Results for ALP Activity

There was only one study comparing a bioceramic material with MTA in terms of ALP activity, and it produced negative results for the bioceramic material studied (Quick-Set2, [31]). The rest of the studies compared two different biomaterials or different concentrations of the same bioceramic material (Table 14).
All studies comparing a bioceramic material and an additive with the bioceramic material itself showed positive significant results for the bioceramic material in combination with the additive (γION-CPC and αION-CPC, [24]; GNP-CPC, [25]; CPC-BGN, [32]; MTA-CaCl2 and MTA-NA2HPO4, [46]), except for one (SC [30]) (Table 15).
The majority of studies comparing a bioceramic material and a control showed positive significant results for the bioceramic materials studied (Gel-HA-TCP, [23]; Zn0/1/2/3, [28]; PR-MTA and Quick-Set2, [31]; SC, [33]; BD, Theracal and MTA, [34]; BD, [38]; CaP, [41]; CSC, [47]; FS and BD [48]; CSP50/100/200, [54]; Ca3SiO5, [57]). One of them showed mixed results depending on the duration of exposure (MTA, [40]) and the remaining two studies showed negative significant results for the bioceramic materials studied (MTA, [36]; MTAP and MTAF, [52]) (Table 16).

3.4.4. Results for Other Bioactivity-Related Analyses

Western blot analyses showed mixed results for Zn0/1/2/3 compared to a control [28], and a higher expression of bioactivity-related markers by PR-MTA compared to Quick-Set2, and by both of them compared to a control [31]. ATR-FTIR showed positive results for PR-MTA compared to Quick-Set2, and for both of them compared to a control [31]. ELISA showed mixed results for MTA and CEM [39]. Assessment of the level of grey in mineralization nodules using Gene Tool showed positive significant results for PLGA/TCP compared to PLGA/HA and PLGA/CDHA [42]. Lastly, both the TRACP & ALP assay kit (Takahara, Shiga, Japan) and the OC and DSP emzyme-linked immunosorbent assay kit (Thermo Fisher Scientific, Waltham, MA, USA) showed that the addition of polydopamine to PR-MTA produced better results than PR-MTA itself.

4. Discussion

The attractiveness of bioceramic materials for their desirable properties added to their constant development, the demand for new advances and the ampliation of treatment indications results in an overflow of related literature over time. Therefore, it seems convenient to establish an updated and organized vision of the commercially available and experimental dentistry-applied bioceramic materials’ characteristics. With this in mind, the aim of this study was to present a systematic review of available literature investigating bioactivity of these materials towards dental pulp stem cells.
In terms of results, it can be highlighted that the most common method used to assess bioactivity in the included studies was the expression of bioactivity-related markers using reverse transcriptase polymerase chain reaction or RT-PCR. A recent systematic review illustrates this tendency by assessing gene expression of dental pulp cells in response to tricalcium silicate cements [58]. Studies also tended to compare new bioceramic materials with the established mineral trioxide aggregate or the more recently introduced Biodentine, as shown in Table 2, in which they appear as the most studied materials.
The use of additives in combination with bioceramic materials looks promising, in some cases enhancing or positively influencing the material’s results in bioactivity assays in comparison with the bioceramic material itself. For example, positive significant results have been shown for iron oxide [24], gold [25], and bioactive glass [32] nanoparticles in combination with calcium phosphate. However, we need to interpret these results with caution, being able to extrapolate them to clinical practice only when a clear dosage or ratio for the additive and bioceramic material has been established in controlled clinical trials.
New material compositions being studied also need to be taken into consideration for future investigations, as some of them have shown positive significant results in bioactivity assays. Novel materials like Exp. PPL [22], Gelatin-HA-TCP [23] and Zinc Bioglass (Zn0/1/2/3) [28] have all shown positive significant results for ARS staining and ALP activity assay compared to a control, and more specifically, Exp. PPL has shown a greater expression of DSPP and OCN compared to MTA and a control; Gelatin-HA-TCP has shown a greater expression of RUNX2, OSX and BSP compared to a control; and Zinc Bioglass (Zn0/1/2/3) has shown a greater expression of RUNX2, ON, CON, MEPE, BSP, and BMP-2 compared to a control. So again, in order to extrapolate these results to clinical practice, it would be interesting to carry out further studies investigating these biomaterials in different conditions.
When assessing quality and risk of bias, included studies referred a similar structural pattern. They reported essential data like a sufficient abstract, a clear objective or objectives, a detailed description of methodology, a mention of the statistical tests used and relevant conclusions; but often failed to justify the sample size used, to describe the randomization process used (if any), and most importantly to address the study’s limitations in the discussion. It may be worth noticing for future reviews that a checklist for reporting in vitro studies or “CRIS” guideline is under development [59] to address the need for uniform methodology in the assessment of this type of studies.
The introduction of new bioceramic materials and the use of additives in combination with them calls for updated research in the field. At the current state, bioactivity assessment of these materials towards dental pulp stem cells centers on in vitro assays or animal research at most. For future studies, it could be interesting to explore the mechanisms with which this bioactivity is achieved and move on towards in vivo trials.

5. Conclusions

Quantification of osteogenic, odontogenic and angiogenic markers using reverse transcriptase polymerase chain reaction or RT-PCR is the prevailing method used to evaluate bioceramic material bioactivity towards DPSCs in the current investigative state, followed by alkaline phosphatase (ALP) enzyme activity assays and Alizarin Red Staining (ARS) to assess mineralization potential. Mineral trioxide aggregate and Biodentine are the prevalent reference materials used to compare with newly introduced bioceramic materials. Available literature compares a wide range of bioceramic materials for bioactivity, consisting majorly of in vitro assays. The desirability of this property added to the rapid introduction of new material compositions makes this subject a clear candidate for future research.

Author Contributions

J.L.S. wrote the paper; L.F., C.L., F.J.R.-L. and S.S. supervised the content.

Funding

This research received no external funding.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Slavkin, H.C.; Bartold, P.M. Challenges and potential in tissue engineering. Periodontol 2000 2006, 41, 9–15. [Google Scholar] [CrossRef] [PubMed]
  2. Kim, S.G.; Malek, M.; Sigurdsson, A.; Lin, L.M.; Kahler, B. Regenerative endodontics: A comprehensive review. Int. Endod. J. 2018, 51, 1367–1388. [Google Scholar] [CrossRef]
  3. Raghavendra, S.S.; Jadhav, G.R.; Gathani, K.M.; Kotadia, P. Bioceramics in endodontics—A review. J. Istanb. Univ. Fac. Dent. 2017, 51, S137. [Google Scholar] [CrossRef] [PubMed]
  4. Jain, P.R.M. The rise of bioceramics in endodontics: A review. Int. J. Pharm. Biol. Sci. 2015, 6, 416–422. [Google Scholar]
  5. Best, S.M.; Porter, A.E.; Thian, E.S.; Huang, J. Bioceramics: Past, present and for the future. J. Eur. Ceram. Soc. 2008, 28, 1319–1327. [Google Scholar] [CrossRef]
  6. Aguilar, P.; Linsuwanont, P. Vital pulp therapy in vital permanent teeth with cariously exposed pulp: A systematic review. J. Endod. 2011, 37, 581–587. [Google Scholar] [CrossRef] [PubMed]
  7. Qureshi, A.; Soujanya, E.; Nandakumar, P. Recent advances in pulp capping materials: An overview. J. Clin. Diagn Res. 2014, 8, 316–321. [Google Scholar] [CrossRef]
  8. Williams, D.F. On the mechanisms of biocompatibility. Biomaterials 2008, 29, 2941–2953. [Google Scholar] [CrossRef] [PubMed]
  9. Enkel, B.; Dupas, C.; Armengol, V.; Apke Adou, J.; Bosco, J.; Daculsi, G.; Jean, A.; Laboux, O.; LeGeros, R.Z.; Weiss, P. Bioactive materials in endodontics. Expert Rev. Med. Devices 2008, 5, 475–494. [Google Scholar] [CrossRef] [PubMed]
  10. Peters, O.A. Research that matters—Biocompatibility and cytotoxicity screening. Int. Endod. J. 2013, 46, 195–197. [Google Scholar] [CrossRef] [PubMed]
  11. Vallittu, P.K.; Boccaccini, A.R.; Hupa, L.; Watts, D.C. Bioactive dental materials—Do they exist and what does bioactivity mean? Dent. Mater. 2018, 34, 693–694. [Google Scholar] [CrossRef]
  12. Bansal, R.; Jain, A. Current overview on dental stem cells applications in regenerative dentistry. J. Nat. Sci. Biol. Med. 2015, 6, 29–34. [Google Scholar] [CrossRef] [PubMed]
  13. Maher, A.; Núñez-Toldrà, R.; Carrio, N.; Ferres-Padro, E.; Ali, H.; Montori, S.; Al Madhoun, A. The effect of commercially available endodontic cements and biomaterials on osteogenic differentiation of dental pulp pluripotent-like stem cells. Dent. J. 2018, 6, 48. [Google Scholar] [CrossRef]
  14. Collado-González, M.; García-Bernal, D.; Oñate-Sánchez, R.E.; Ortolani-Seltenerich, P.E.; Álvarez-Muro, T.; Lozano, A.; Forner, L.; Llena, C.; Moraleda, J.M.; Rodríguez-Lozano, F.J. Cytotoxicity and bioactivity of various pulpotomy materials on stem cells from human exfoliated primary teeth. Int. Endod. J. 2017, 50, e30. [Google Scholar] [CrossRef]
  15. Rodrigues, E.M.; Cornélio, A.L.G.; Mestieri, L.B.; Fuentes, A.S.C.; Salles, L.P.; Rossa-Junior, C.; Faria, G.; Guerreiro-Tanomaru, J.M.; Tanomaru-Filho, M. Human dental pulp cells response to mineral trioxide aggregate (MTA) and MTA plus: Cytotoxicity and gene expression analysis. Int. Endod. J. 2017, 50, 780–789. [Google Scholar] [CrossRef] [PubMed]
  16. Bakhtiar, H.; Nekoofar, M.H.; Aminishakib, P.; Abedi, F.; Naghi Moosavi, F.; Esnaashari, E.; Azizi, A.; Esmailan, S.; Ellini, M.R.; Mesgarzadeh, V.; et al. Human pulp responses to partial pulpotomy treatment with TheraCal as compared with biodentine and ProRoot MTA: A clinical trial. J. Endod. 2017, 43, 1786–1791. [Google Scholar] [CrossRef]
  17. Escobar-García, D.M.; Aguirre-López, E.; Méndez-González, V.; Pozos-Guillén, A. Cytotoxicity and initial biocompatibility of endodontic biomaterials (MTA and biodentine™) used as root-end filling materials. Biomed Res. Int. 2016, 2016, 7926961. [Google Scholar] [CrossRef]
  18. Moher, D.; Shamseer, L.; Clarke, M.; Ghersi, D.; Liberati, A.; Petticrew, M.; Shekelle, P.; Stewart, L.; PRISMA-P Group. Preferred reporting items for systematic review and meta-analysis protocols (PRISMA-P) 2015 statement. Syst. Rev. 2015, 4, 1. [Google Scholar] [CrossRef] [PubMed]
  19. Faggion, C.M. Guidelines for reporting pre-clinical in vitro studies on dental materials. J. Evid. Based Dent. Pract. 2012, 12, 182–189. [Google Scholar] [CrossRef] [PubMed]
  20. Kilkenny, C.; Browne, W.J.; Cuthill, I.C.; Emerson, M.; Altman, D.G. Improving bioscience research reporting: The ARRIVE guidelines for reporting animal research. PLoS Biol. 2010, 8, e1000412. [Google Scholar] [CrossRef]
  21. Hanafy, A.K.; Shinaishin, S.F.; Eldeen, G.N.; Aly, R.M. Nano hydroxyapatite & mineral trioxide aggregate efficiently promote odontogenic differentiation of dental pulp stem cells. Open Access Maced. J. Med. Sci. 2018, 6, 1727. [Google Scholar] [CrossRef]
  22. Pedano, M.S.; Li, X.; Li, S.; Sun, Z.; Cokic, S.M.; Putzeys, E.; Yoshihara, K.; Yoshida, Y.; Chen, Z.; Van Landuyt, K. Freshly-mixed and setting calcium-silicate cements stimulate human dental pulp cells. Dent. Mater. 2018, 34, 797–808. [Google Scholar] [CrossRef] [PubMed]
  23. Gu, Y.; Bai, Y.; Zhang, D. Osteogenic stimulation of human dental pulp stem cells with a novel gelatin-hydroxyapatite-tricalcium phosphate scaffold. J. Biomed. Mater. Res. A 2018, 106, 1851–1861. [Google Scholar] [CrossRef] [PubMed]
  24. Xia, Y.; Chen, H.; Zhang, F.; Wang, L.; Chen, B.; Reynolds, M.A.; Ma, J.; Schneider, A.; Gu, N.; Xu, H.H.K. Injectable calcium phosphate scaffold with iron oxide nanoparticles to enhance osteogenesis via dental pulp stem cells. Artif. Cells Nanomed. Biotechnol. 2018, 46, 433. [Google Scholar] [CrossRef] [PubMed]
  25. Xia, Y.; Chen, H.; Zhang, F.; Bao, C.; Weir, M.D.; Reynolds, M.A.; Ma, J.; Gu, N.; Xu, H.H.K. Gold nanoparticles in injectable calcium phosphate cement enhance osteogenic differentiation of human dental pulp stem cells. Nanomedicine 2018, 14, 35–45. [Google Scholar] [CrossRef] [PubMed]
  26. Kyung-Jung, K.; Min Suk, L.; Chan-Woong, M.; Jae-Hoon, L.; Hee Seok, Y.; Young-Joo, J. In vitro and in vivo dentinogenic efficacy of human dental pulp-derived cells induced by demineralized dentin matrix and HA-TCP. Stem Cells Int. 2017, 2017, 4–15. [Google Scholar] [CrossRef]
  27. Wongsupa, N.; Nuntanaranont, T.; Kamolmattayakul, S.; Thuaksuban, N. Assessment of bone regeneration of a tissue-engineered bone complex using human dental pulp stem cells/poly(ε-caprolactone)-biphasic calcium phosphate scaffold constructs in rabbit calvarial defects. J. Mater. Sci.: Mater. Med. 2017, 28, 1–14. [Google Scholar] [CrossRef] [PubMed]
  28. Huang, M.; Hill, R.G.; Rawlinson, S.C.F. Zinc bioglasses regulate mineralization in human dental pulp stem cells. Dent. Mater. 2017, 33, 543–552. [Google Scholar] [CrossRef]
  29. Atalayin, C.; Tezel, H.; Dagci, T.; Karabay Yavasoglu, N.U.; Oktem, G.; Kose, T. In vivo performance of different scaffolds for dental pulp stem cells induced for odontogenic differentiation. Braz. Oral. Res. 2016, 30, e120. [Google Scholar] [CrossRef]
  30. Theocharidou, A.; Bakopoulou, A.; Kontonasaki, E.; Papachristou, E.; Hadjichristou, C.; Bousnaki, M.; Theodorou, G.; Papadopoulou, L.; Kantiranis, N.; Paraskevopoulos, K. Odontogenic differentiation and biomineralization potential of dental pulp stem cells inside mg-based bioceramic scaffolds under low-level laser treatment. Lasers Med. Sci. 2017, 32, 201–210. [Google Scholar] [CrossRef] [PubMed]
  31. Niu, L.N.; Pei, D.D.; Morris, M.; Jiao, K.; Huang, X.Q.; Primus, C.M.; Susin, F.L.; Bergeron, B.E.; Pashley, D.H.; Tay, F.R. Mineralogenic characteristics of osteogenic lineage-committed human dental pulp stem cells following their exposure to a discoloration-free calcium aluminosilicate cement. Dent. Mater. 2016, 32, 1235–1247. [Google Scholar] [CrossRef] [PubMed]
  32. Lee, S.I.; Lee, E.S.; El-Fiqi, A.; Lee, S.Y.; Eun-Cheol, K.; Kim, H.W. Stimulation of odontogenesis and angiogenesis via bioactive nanocomposite calcium phosphate cements through integrin and VEGF signaling pathways. J. Biomed. Nanotechnol. 2016, 12, 1048–1062. [Google Scholar] [CrossRef] [PubMed]
  33. Bakopoulou, A.; Papachristou, E.; Bousnaki, M.; Hadjichristou, C.; Kontonasaki, E.; Theocharidou, A.; Papadopoulou, L.; Kantiranis, N.; Zachariadis, G.; Leyhausen, G. Human treated dentin matrices combined with zn-doped, mg-based bioceramic scaffolds and human dental pulp stem cells towards targeted dentin regeneration. Dent. Mater. 2016, 32, e175. [Google Scholar] [CrossRef] [PubMed]
  34. Bortoluzzi, E.A.; Niu, L.; Palani, C.D.; El-Awady, A.R.; Hammond, B.D.; Pei, D.D.; Tian, F.C.; Cutler, C.W.; Pashley, D.H.; Tay, F.R. Cytotoxicity and osteogenic potential of silicate calcium cements as potential protective materials for pulpal revascularization. Dent. Mater. 2015, 31, 1510–1522. [Google Scholar] [CrossRef]
  35. Natu, V.P.; Dubey, N.; Loke, G.C.L.; Tan, T.S.; NG, W.H.; Yong, C.W.; Cao, T.; Rosa, V. Bioactivity, physical and chemical properties of MTA mixed with propylene glycol. J. Appl. Oral Sci. 2015, 23, 405–411. [Google Scholar] [CrossRef]
  36. Widbiller, M.; Lindner, S.; Buchalla, W.; Eidt, A.; Hiller, K.A.; Schmalz, G.; Galler, K.M. Three-dimensional culture of dental pulp stem cells in direct contact to tricalcium silicate cements. Clin. Oral Investig. 2016, 20, 237–246. [Google Scholar] [CrossRef]
  37. Zhu, L.; Yang, J.; Zhang, J.; Lei, D.; Xiao, L.; Cheng, X.; Lin, Y.; Peng, B. In vitro and in vivo evaluation of a nanoparticulate bioceramic paste for dental pulp repair. Acta Biomater. 2014, 10, 5156–5168. [Google Scholar] [CrossRef] [PubMed]
  38. Luo, Z.; Kohli, M.R.; Yu, Q.; Kim, S.; Qu, T.; He, W.X. Biodentine induces human dental pulp stem cell differentiation through mitogen-activated protein kinase and calcium-/calmodulin-dependent protein kinase II pathways. J. Endod. 2014, 40, 937–942. [Google Scholar] [CrossRef]
  39. Asgary, S.; Nazarian, H.; Khojasteh, A.; Shokouhinejad, N. Gene expression and cytokine release during odontogenic differentiation of human dental pulp stem cells induced by 2 endodontic biomaterials. J. Endod. 2014, 40, 387–392. [Google Scholar] [CrossRef] [PubMed]
  40. Wang, Y.; Yan, M.; Fan, Z.; Ma, L.; Yu, Y.; Yu, J. Mineral trioxide aggregate enhances the odonto/osteogenic capacity of stem cells from inflammatory dental pulps via NF-κB pathway. Oral. Dis. 2014, 20, 650–658. [Google Scholar] [CrossRef]
  41. Nam, S.; Won, J.; Kim, C.H.; Kim, H.W. Odontogenic differentiation of human dental pulp stem cells stimulated by the calcium phosphate porous granules. J. Tissue Eng. 2011, 2011, 812547. [Google Scholar] [CrossRef]
  42. Zheng, L.; Yang, F.; Shen, H.; Hu, X.; Mohizuki, C.; Sato, M.; Wang, S.; Zhang, Y. The effect of composition of calcium phosphate composite scaffolds on the formation of tooth tissue from human dental pulp stem cells. Biomaterials 2011, 32, 7053–7059. [Google Scholar] [CrossRef] [PubMed]
  43. Zhao, X.; He, W.; Song, Z.; Tong, Z.; Li, S.; Ni, L. Mineral trioxide aggregate promotes odontoblastic differentiation via mitogen-activated protein kinase pathway in human dental pulp stem cells. Mol. Biol. Rep. 2012, 39, 215–220. [Google Scholar] [CrossRef] [PubMed]
  44. Paranjpe, A.; Zhang, H.; Johnson, J.D. Effects of mineral trioxide aggregate on human dental pulp cells after pulp-capping procedures. J. Endod. 2010, 36, 1042–1047. [Google Scholar] [CrossRef] [PubMed]
  45. Tu, M.G.; Ho, C.C.; Hsu, T.T.; Huang, T.H.; Lin, M.J.; Shie, M.Y. Mineral trioxide aggregate with mussel-inspired surface nanolayers for stimulating odontogenic differentiation of dental pulp cells. J. Endod. 2018, 44, 963–970. [Google Scholar] [CrossRef]
  46. Kulan, P.; Karabiyik, O.; Kose, G.T.; Kargul, B. The effect of accelerated mineral trioxide aggregate on odontoblastic differentiation in dental pulp stem cell niches. Int. Endod. J. 2018, 51, 758–766. [Google Scholar] [CrossRef] [PubMed]
  47. Xu, C.; Wen, Y.; Zhou, Y.; Zhu, Y.; Dou, Y.; Huan, Z.; Chang, J. In vitro self-setting properties, bioactivity, and antibacterial ability of a silicate-based premixed bone cement. Int. J. Appl. Ceram. Technol. 2018, 15, 460–471. [Google Scholar] [CrossRef]
  48. Sun, Y.; Luo, T.; Shen, Y.; Haapasalo, M.; Zou, L.; Liu, J. Effect of iRoot fast set root repair material on the proliferation, migration and differentiation of human dental pulp stem cells in vitro. PLoS ONE 2017, 12, e0186848. [Google Scholar] [CrossRef]
  49. Lee, B.; Lee, B.; Chang, H.; Hwang, Y.; Hwang, I.; Oh, W. Effects of a novel light-curable material on odontoblastic differentiation of human dental pulp cells. Int. Endod. J. 2017, 50, 464–471. [Google Scholar] [CrossRef]
  50. Daltoé, M.O.; Paula-Silva, F.W.; Faccioli, L.H.; Gatón-Hernández, P.M.; De Rossi, A.; Bezerra Silva, L.A. Expression of mineralization markers during pulp response to biodentine and mineral trioxide aggregate. J. Endod. 2016, 42, 596–603. [Google Scholar] [CrossRef] [PubMed]
  51. Gandolfi, M.; Spagnuolo, G.; Siboni, F.; Procino, A.; Riviecco, V.; Pelliccioni, G.A.; Prati, C.; Rengo, S. Calcium silicate/calcium phosphate biphasic cements for vital pulp therapy: Chemical-physical properties and human pulp cells response. Clin. Oral Investig. 2015, 19, 2075–2089. [Google Scholar] [CrossRef]
  52. Mestieri, L.B.; Gomes-Cornélio, A.L.; Rodrigues, E.M.; Salles, L.P.; Bosso-Martelo, R.; Guerreiro-Tanomaru, J.M.; Filho, M.T. Biocompatibility and bioactivity of calcium silicate-based endodontic sealers in human dental pulp cells. J. Appl. Oral Sci. 2015, 23, 467–471. [Google Scholar] [CrossRef] [PubMed]
  53. AbdulQader, S.T.; Kannan, T.P.; Rahman, I.A.; Ismail, H.; Mahmood, Z. Effect of different calcium phosphate scaffold ratios on odontogenic differentiation of human dental pulp cells. Mater. Sci. Eng. C Mater. Biol. Appl. 2015, 49, 225–233. [Google Scholar] [CrossRef] [PubMed]
  54. Zhang, X.; Wu, C.; Chang, J.; Sun, J. Odontogenic differentiation of human dental pulp cells induced by silicate-based bioceramics via activation of P38/MEPE pathway. RSC Adv. 2015, 5, 72536–72543. [Google Scholar] [CrossRef]
  55. Lee, S.-Y.; Yun, H.-M.; Perez, R.-A.; Gallinetti, S.; Ginebra, M.-P.; Choi, S.-J.; Kim, E.-C.; Kim, H.-W. Nanotopological-tailored calcium phosphate cements for the odontogenic stimulation of human dental pulp stem cells through integrin signaling. RSC Adv. 2015, 5, 63363–63371. [Google Scholar] [CrossRef]
  56. Öncel Torun, Z.; Torun, D.; Demirkaya, K.; Yavuz, S.T.; Elçi, M.P.; Sarper, M.; Avcu, F. Effects of iRoot BP and white mineral trioxide aggregate on cell viability and the expression of genes associated with mineralization. Int. Endod. J. 2015, 48, 986–993. [Google Scholar] [CrossRef] [PubMed]
  57. Peng, W.; Liu, W.; Zhai, W.; Jiang, L.; Li, L.; Chang, J.; Zhu, Y. Effect of tricalcium silicate on the proliferation and odontogenic differentiation of human dental pulp cells. J. Endod. 2011, 37, 1240–1246. [Google Scholar] [CrossRef] [PubMed]
  58. Rathinam, E.; Rajasekharan, S.; Chitturi, R.T.; Martens, L.; De Coster, P. Gene expression profiling and molecular signaling of dental pulp cells in response to tricalcium silicate cements: A Systematic review. J. Endod. 2015, 41, 1805–1817. [Google Scholar] [CrossRef]
  59. Krithikadatta, J.; Gopikrishna, V.; Datta, M. CRIS guidelines (checklist for reporting in-vitro studies): A concept note on the need for standardized guidelines for improving quality and transparency in reporting in-vitro studies in experimental dental research. J. Conserv. Dent. 2014, 17, 301–304. [Google Scholar] [CrossRef]

Article Metrics

Citations

Article Access Statistics

Journal Statistics
Multiple requests from the same IP address are counted as one view.
Download PDF
Limit Equilibrium Method-based Shear Strength Prediction for Corroded Reinforced Concrete Beam with Inclined Bars
Previous
Application of Nanoindentation and 2D and 3D Imaging to Characterise Selected Features of the Internal Microstructure of Spun Concrete
Next