Abstract
Objectives
Dentin tissue can act as a reservoir for bioactive molecules that create signals for cellular proliferation and differentiation to initiate tissue regeneration. Therefore, the aim of this study is to compare the cell viability, inflammatory response, and antimicrobial activity of bovine dentin grain-added calcium-hydroxide (CH-BDG) with different pulp-capping materials.
Methods
ProRoot MTA, Biodentine, Dycal, TheraCal-LC, and an experimental material, CH-BDG, were examined. Cell viability was determined via the WST-1 assay. The inflammatory response was analysed by the monocyte chemoattractant protein-1 (MCP-1/CCL2) and macrophage inflammatory protein-1α (MIP-1α/CCL3) levels. The antimicrobial activity was evaluated by agar-diffusion.
Results
The cell viability of CH-BDG was analogous with Biodentine and control at 24 h. The cell viability of CH-BDG decreased at 48 h, but the rate was higher than ProRoot MTA and Dycal (p<0.05). For MCP-1 and MIP-1α values, there was no significant difference between the control and CH-BDG. The MCP-1 level of CH-BDG was lower compared to other pulp-capping materials (p<0.05). The MIP-1α level of CH-BDG was lower compared to ProRoot MTA, Biodentine, and TheraCal-LC (p<0.05). No inhibition zone was detected against oral microorganisms for CH-BDG.
Conclusions
The experimentally developed CH-BDG showed competing properties and additional advantages compared to the existing pulp-capping materials.
Keywords: biomaterial; biocompatibility; chemokine level; experimental material; pulp capping
Introduction
The exposed pulp tissue covered with a biomaterial promotes the formation of a dentin-like structure to maintain the vital functions and entirety of the pulp-dentin complex in pulp-capping [1]. The majority of the pulp-capping agents contain calcium, which is a substantial bioactive component. Calcium hydroxide has been applied for reparative dentin formation, induction of mineralisation, inhibition of bacterial growth and maintenance of pulp vitality as a gold standard in the long term [2]. However, it has disadvantages such as poor mechanical properties, dissolution over time, insufficient adhesion to dentin, inability to provide sufficient biological cover, multiple tunnel defects in dentin bridge formation and ultimately the development of bacterial infection [1]. In this context, the main target for new pulp-capping materials is to benefit from the existing advantages of calcium hydroxide and to eliminate its negative properties. The calcium hydroxide cements, which are widely used in clinical practice, have been developed against the deficits of calcium hydroxide in powder form, such as difficulty getting hard and solubility. Although the difficulty of setting is solved in calcium hydroxide cement, it has disadvantages, such as dissolving over time and being more toxic due to disalicylate, accelerator, and plasticiser additives [3].
Mineral trioxide aggregate (MTA), glass-ionomer cement, tricalcium silicate-containing materials, resin-modified MTA, and resin-based materials have been developed to overcome these disadvantages. MTA exhibits many properties similar to calcium hydroxide, such as biocompatibility, high alkalinity, antibacterial activity, radiopacity, release of dentin matrix proteins and more effective sealing [4]. However, it has disadvantages such as the potential for discoloration, difficulty in application/manipulation and the longer time required to complete the setting. A new calcium silicate-based material, Biodentine, has been developed via MTA-based technology with properties such as easy application, shorter setting time and good physical properties [5]. Biodentine decomposes into a calcium silicate-based gel and calcium hydroxide upon contact with body fluids, and a hydroxyapatite-like structure is formed as a result of the contact of calcium hydroxide with phosphate ions. In addition, the metallic residues are eliminated during production, and the inflammation caused by the material is at a tolerable minimum level [6]. Biodentine is a mechanically stronger, less soluble and better-sealing material compared to the previous gold standard material, calcium hydroxide [7]. Resin-modified calcium silicate-filled pulp-capping material has advantages such as providing adequate coverage and easy application [8]. However, compared to Biodentine, the resin-modified calcium silicate-filled pulp-capping material has a lower repair capacity [9, 10].
Dentin tissue has been reported to be a source for the release of dentinogenesis-related proteins and ensuring regulation during dentin development and regeneration [11]. Dentin derivatives could serve as a promising natural substitute for direct pulp-capping to ensure dentin regeneration and maintaining of pulp vitality [11]. Bovine dentin grain could be evaluated as an easily accessible dentin tissue source. Therefore, the development of new pulp-capping agents by using this source may provide a cost-effective alternative to the existing products. In this study, we compared the main biological properties of an experimental material, bovine dentin grain added calcium hydroxide (CH-BDG), with different pulp-capping materials. The tested null hypothesis stated that there were no statistical differences among the cell viability, chemokine levels and antimicrobial activity of the tested materials.
Materials and methods
Preparation of the specimens
Four different pulp-capping materials (ProRoot MTA, Dentsply, Tulsa Dental, OK, USA; Biodentine, Septodont, Saint Maur des Fosses, France; Dycal, Dentsply Tulsa, Johnson City, TN, USA and TheraCal LC, Bisco Schaumburg, IL, USA) and an experimental material CH-BDG were examined. The disc-shaped samples with 8 x 2 mm in plastic blocks were generated in accordance with the manufacturer’s recommendations (n=6). The prepared samples were kept under UV light for 15 min for sterilisation.
Preparation of CH-BDG
The extracted bovine incisor teeth (n=30) provided slaughterhouse material were used to obtain dentin grain (Approval from the Animal Experiments Ethics Committee of Ege University, Approval Code: 2019-065). The root was cut from the apical third, and the pulp tissue was removed using a stainless-steel file from the apical foramen. The periodontal ligament tissue, together with a part of cementum, was scraped away using a curette, and the teeth were stored in 0.1 % thymol solution at room temperature until the experimental procedures. Standardised cylindrical cavities were prepared on the vestibular surfaces of teeth crowns using an aerator and diamond ring and fissure burs under water cooling. The depth of the cavities was created to avoid exposure in the pulp chamber and perforation of the palatal wall. After the tooth surfaces were dried with air spray, dentin grains were obtained from the prepared cavities using a low-speed contra-angle handpiece and tungsten-carbide round bur. Dentin grains were collected in sterile tubes (Supplementary Figure1). Particle size was measured with Zetasizer (Malvern Panalytical) in the range of 1–10 µm (Supplementary Figure2), exhibiting a polydisperse structure (polydispersity index=0.9–1.0).
A modified powder mixture was obtained by mixing calcium hydroxide powder (Saver-Pyrax, Haridwar, Uttarakhand, India) and dentin grains obtained from bovine teeth at 1/1 by weight. The hom*ogenisation of the mixture was achieved by vortexing. The paste was obtained by mixing the powder mixture with liquid (distilled water), and the samples were prepared in accordance with the study design.
Cell viability test
L929 mouse fibroblast cells (ATCC, CCL-1) were cultured with RPMI 1640 (Sigma-Aldrich), 10 % fetal bovine serum (Gibco Invitrogen), 1 % l-glutamine (Sigma-Aldrich) and 100 units/mL of penicillin/streptomycin (Gibco Invitrogen). The specimens were placed in 48-well as one sample per well and incubated (1x104 cells/well) for 24 and 48 h. The cells without any application were considered as the control group. Cell viability was measured by the WST-1 method (Premix WST-1 Cell Proliferation Assay System/Takara Bio. Inc., Shiga, Japan). The experiments were carried out in triplicate. The results were reported as the mean absorption±standard deviation expressed as % control.
Measurement of chemokine levels
The cell culture supernatants were collected and centrifuged at 10.000 g for 10 min after 24 and 48 h of incubation periods. The experiments were carried out in triplicate. Monocyte chemoattractant protein 1 (MCP-1) and macrophage inflammatory protein-1α (MIP-1α) levels were measured by mouse CCL2/JE/MCP-1 ELISA kit (FineTest, Wuhan Fine Biotech. Co., Ltd., China) (Analytical measurement range: 15.625–1,000 pg/mL) and mouse CCL3/MIP-1 alpha ELISA kit (FineTest, Wuhan Fine Biotech. Co., Ltd., China) (Analytical measurement range: 15.625–1,000 pg/mL) according to the manufacturer’s instructions. The intra-assay and inter-assay coefficients of variation (CVs) of kits were <8 % and <10 %, respectively.
Antimicrobial activity test
The antimicrobial activity of the materials against oral microorganisms was evaluated by agar-diffusion. The disc-shaped samples (8×2 mm) were prepared according to the manufacturers’ instructions, and the materials were tested after completing setting reactions (n=6). Separate Petri dishes were used for each microorganism and each material. The agar medium (20 mL) was poured into 9 cm diameter sterile petri dishes to create 5 mm thickness and left to solidify. Then, the overnight active liquid cultures of oral microorganisms (5.8×106 cfu/mL) were spread on the medium surface, and the standard wells were created in the medium with the blunt tip of the Pasteur pipette. The material specimens were placed in the standard wells. Streptococcus mutans (DSM20523), Lactobacillus acidophilus (DSM 20079) and Enterococcus faecalis (ATCC 29212) strains were used. In order to prevent possible material diffusion and interaction on the agar surface, no additional material was included in the experimental design to form the control group in the same petri dish. The sterile paper discs were used in the control group. Only one type of microorganism and one type of material were tested in each petri dish. The inhibition zone around each well was randomly measured from two points (with two technical replicates) via a digital caliper (Mitutoya Absolute Digimatic Caliper, Mitutoya Corp, Kanogawa, Japan) after 24 and 48 h. The mean value (mm) was obtained and recorded for each specimen. The lack of an inhibition zone (0 mm) was estimated as the absence of antimicrobial activity.
Statistical analysis
Statistical analysis was performed with GraphPad Prism five for Windows Version 5.05 (La-Jolla). A one-way ANOVA test was applied for statistical analysis of cell viability and chemokine levels data. Student’s t-test was used for pairwise comparisons within groups. A statistically significant level was determined as p<0.05.
Results
Cell viability
The lowest cell viability rate was detected in ProRoot MTA (32.1±6.6 %) and Dycal (27.6±5.6 %) groups at 24 h compared to the control (p<0.05) (Figure1). The situation was similar with the lowest cell viability rates in ProRoot MTA (6.5±0.7 %) and Dycal (7.1±1.1 %) groups at 48 h compared to the control (p<0.05) (Figure1). At 24 h, the cell viability rate of CH-BDG (94.1±21.2 %) was similar to the control group (p=0.7386). On cells at 24 h, the effect of the CH-BDG (94.1±21.2 %) was close to the effect of Biodentine (91.5±19.8 %) (p=0.8878) and ThereCal (96.4±6.1 %) (p=0.8633). The cell viability of CH-BDG at 48 h (37.8±12.8 %) decreased compared to the cell viability rate at 24 h (94.1±21.2 %) (p<0.05). At 48 h, the cell viability was found to be higher in CH-BDG (37.8±12.8 %) compared to ProRoot MTA (6.5±0.7 %) and Dycal (7.1±1.1 %) (p<0.05).
Figure1:
The cell viability levels after 24 and 48 h incubation. *Statistical significant difference vs. ProRoot MTA (48 h) and Dycal (48 h).
Chemokine levels
Chemokine levels after 24 and 48 h were presented in Figures2 and 3. For MCP-1 and MIP-1α values, there was no significant difference between the control and CH-BDG in both time intervals. The highest MCP-1 value was detected in the ProRoot MTA and TheraCal LC groups compared to the control group at 24 and 48 h (p<0.05). The MCP-1 level of CH-BDG was lower compared to other pulp-capping materials (ProRoot MTA, Biodentine, Dycal and TheraCal LC) for both time intervals (p<0.05). The MIP-1α level of CH-BDG was lower compared to ProRoot MTA, Biodentine and TheraCal LC at 24 and 48 h (p<0.05).
Figure2:
The chemokine (MCP-1) levels after 24 and 48 h. *Statistical significant difference compared to material exposed cells.
Figure3:
The chemokine (MIP-1α) levels after 24 and 48 h. *Statistical significant difference compared to ProRoot MTA, Biodentine and ThereCal LC.
Antimicrobial activity
Considering the inhibition zones (Figure4), a limited inhibition zone (17±1.3 mm) against S.mutans was detected only in the Dycal group. The inhibition zone formed at 24 h did not change at 48 h. In other groups, the formation of an inhibition zone was not observed.
Figure4:
Inhibition zones formed after 48 h.
Discussion
Four different pulp-capping materials and an experimental material, CH-BDG, were evaluated, and the null hypothesis was rejected. Differences were verified among the cell viability, chemokine levels, and antimicrobial activity of the tested materials.
Dentin tissue has been reported to act as a reservoir for bioactive molecules formed by odontoblasts and fibroblasts [12, 13]. These molecules create signals for cellular proliferation and differentiation to initiate tissue regeneration [13, 14]. The inductivity of autogenous teeth has been related to dentin tissue as a suitable source for different signalling molecules [14, 15]. The first choice is autologous sources obtained from the patient’s own tissues, but it is not always possible to obtain autologous dentin derivatives. Due to limited allogenic resources, there is a need for xenogenic dentin and different primates to meet clinical demand in the future [16]. Different sources, such as porcine and dogs have been used to obtain dentin matrix [16, 17]. In this study, calcium hydroxide was modified with the combination of bovine dentin grain to benefit from the existing advantages of calcium hydroxide (the main active ingredient of current pulp-capping agents) and the potential inductive properties of dentin tissue. Bovine teeth were preferred due to their similarity to human tooth tissue, easy accessibility, cost-effectiveness and no ethical problems. The incisors were preferred for their advantages, such as easy removal from the alveolar socket of the bovine skull bone and the ability to obtain large amounts of dentin grain due to its large size. The chemical or physical removal of the cellular compartment of living tissues, identified as the decellularization procedure, effectively reduces the immunogenicity in grafts [16]. Therefore, the pulp tissue and surrounding soft tissue were removed mechanically. However, it may be necessary to remove the organic part to avoid the risk of tissue rejection or infection. Since the dentin grains are solid material, they were mixed with calcium hydroxide powder to manipulate them for pulp capping, and the obtained powder was mixed with liquid to form a paste.
The primary properties expected from pulp-capping material are to maintain pulp vitality and biocompatibility [18]. Accordingly, WST-1 analysis was used to determine the effects of the materials on cell viability. MTA has been reported to be less toxic, easier to use and causes less pulpal inflammation than calcium hydroxide [19]. While cytotoxicity was not observed in MTA-treated rat pulp cells, exposure to Dycal has been reported to result in viability loss [20]. In this study, the lowest cell viability was observed in ProRoot MTA and Dycal. In our study, TheraCal LC decreased cell viability after 48 h and showed a lower cell viability profile compared to Biodentine. TheraCal LC has been determined to show similar/lower cytotoxicity to Dycal on mouse odontoblast cells and human pulp stem cells, but it has been reported to be more cytotoxic than calcium silicates without resin, such as Biodentine, MTA Angelus and ProRoot MTA. However, it was stated that this cytotoxicity may be due to unpolymerised monomers in the oxygen inhibition layer on the surface of TheraCal LC test specimens during sample preparation [21]. In this study, cell viability in ThereCal LC-exposed cells was higher than in ProRoot MTA and Dycal. Although cell viability tended to decrease at 48 h in CH-BDG, it was higher when compared to ProRoot MTA and Dycal.
Inflammation is the main protective response to any harm in the body, and a high inflammatory response indicates exposure to a harmful agent or substance. After the stimulation by inflammatory mediators, fibroblasts are activated to produce cytokines and soluble growth factors to direct inflammatory and reparative responses. The studies have mainly focused on the interleukin levels of pulp-capping materials, and different chemokine levels have been determined [22, 23]. However, it is critical to consider that studies evaluating multiple chemokine levels simultaneously will provide more information about the effects of pulp-capping materials on the inflammatory process. Chemokines are small cytokines that play a role in the activation of immune system cells. MCP-1 is one of the key chemokines that regulate the migration and infiltration of monocytes/macrophages. It has a vital role in the inflammation process, where it attracts or enhances the expression of other inflammatory factors or cells [24]. MIP-1α is a chemotactic chemokine secreted by macrophages, and it may have diagnostic potential for the detection of several inflammatory situations [25]. In this experimental model, MCP-1 and MIP-1α levels, which are chemokines that commonly exist in fibroblasts, were examined. It is desirable to produce a low inflammatory response for ideal pulp-capping material. Incomplete hydration of TheraCal LC causes monomer leakage, leading to toxicity of pulp cells [26]. The non-toxic concentrations of monomers may inhibit the secretion of the components involved in the mineralisation process, like dentin sialoproteins and osteonectin [27]. TheraCal LC causes dentin bridge formation with mild chronic inflammation due to its hydration properties; it presents decreased dentin bridge thickness and higher inflammation [9]. TheraCal LC has been shown to be toxic to pulp fibroblasts with a higher inflammatory effect and a lower repair capacity than Biodentine [9, 10]. In this study, TheraCal LC induced a higher inflammatory response than other materials. The MIP-1α level was significantly lower in CH-BDG compared to ProRoot MTA and Biodentine.
Another feature expected from an ideal pulp-capping material is to present and sustain antimicrobial properties to protect the pulp tissue against secondary infection caused by microleakage or residual bacteria [28]. In the mineralisation process after pulp-capping, the period of three weeks is critical considering the high dentin matrix protein expressions [29]. Although studies have focused on the antibacterial activity of freshly mixed pulp-capping materials [30], it is important to maintain antibacterial activity during the mineralisation and hard tissue formation processes. Therefore, the antibacterial activity of materials after setting reaction was evaluated in this study. The agar diffusion method, which is the basic, simple and traditional method used to evaluate the antimicrobial activity of materials [31], was applied. The diffusion capacity of the examined materials to the agar surface may affect the size of inhibition zones and, eventually, the test results. In this study, the antibacterial activities of different materials as solid form after completed setting reaction were investigated to eliminate the mentioned contingency. A stable, measurable inhibition zone against S.mutans was established only in the Dycal group. Dycal was reported to be the most effective material against Streptococcus strains, and Biodentine did not form an inhibition zone against S.mutans [28]. The antibacterial activity of Dycal may be associated with the release of hydroxyl radicals and an increase in pH [32]. This can be attributed to the solubility and cytotoxicity of Dycal. In a study regarding the antibacterial activity against E.faecalis, Dycal showed the lowest effect, the activity of Biodentine remained at the same level for a week, and the antibacterial activity of MTA decreased [33]. The difference between findings may be related to methods such as the direct contact test in the mentioned study and the agar diffusion test of set materials completing the setting reaction in this study. MTA products present antibacterial activity against S.mutans but not against E.faecalis [30]. Moreover, decreased antibacterial efficacy has been reported after the reaction has occurred [34]. The antibacterial properties of Biodentine and MTA are associated with high alkaline pH values, which have an inhibitory effect on microorganism growth and cause dentin disinfection [35]. However, Biodentine and MTA groups did not show any antibacterial activity against oral microorganisms included in this study. Moreover, CH-BDG did not cause any antimicrobial activity. In future studies, it may be useful to investigate the antimicrobial activity of the materials by different methods.
In the limitation of this invitro study, the key parameters related to biological properties such as cell viability, inflammatory response and antimicrobial effect were comparatively studied on multiple pulp-capping materials and an overall profile was defined as multiple parameters were evaluated simultaneously. Among the tested materials, the experimentally developed CH-BDG exhibited both higher cell viability rates and lower MCP-1 and MIP-1α levels. Therefore, CH-BDG seems to exhibit competing properties and additional advantages in terms of cell viability and chemokine levels compared to the existing pulp-capping materials. In this way, preliminary information has been obtained for further research regarding the usability of dentin grain obtained from bovine teeth. The developed material may be used for direct pulp-capping or other vital regenerative treatments such as apexogenesis and amputation, but further studies are needed to identify the mechanical properties of CH-BDG. The key advantages of this material can be summarised as follows: obtaining from an accessible source, not creating ethical problems, easy to apply, affordable cost, exhibiting advantages compared to alternative materials in terms of tested biological parameters, the possibility of its modification and improvement of its features. The dentin grain may be produced to nanoparticle size, and various agents such as growth factors, antioxidant compounds, and surface active antibacterial compounds can be added. The experimental material may be converted into gel form to facilitate the application. In this way, clinical usage potential can be increased by improving the properties of the current prototype with further investigations.
Corresponding author: Cigdem Atalayin Ozkaya, Department of Restorative Dentistry, School of Dentistry, Ege University, Ankara Street, Izmir 35100, Türkiye, E-mail: dtcatalayin@gmail.com
Funding source: Ege University Research Foundation
Award Identifier / Grant number: TGA-2019-20905
Acknowledgments
This project was supported by the Ege University Scientific Research Projects Coordinatorship (Project No: TGA-2019-20905). We would like to thank the Ege University Scientific Research Projects Coordinatorship for providing the necessary financial support for the realisation of the research.
Research ethics: The Ethical Approval was obtained from the Animal Experiments Ethics Committee of Ege University (Approval Code: 2019-065).
Informed consent: Informed consent was obtained from all individuals included in this study.
Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission. 1. Substantial contributions to the conception or design of the work; or the acquisition, analysis, or interpretation of data for the work; Cigdem Atalayin Ozkaya, Guliz Armagan, Dilek Akin, Dervis Birim, Mustafa Ates, Taner Dagci, Huseyin Tezel. 2. Drafting the work or revising it critically for important intellectual content; Cigdem Atalayin Ozkaya, Guliz Armagan, Dilek Akin. 3. Final approval of the version to be published; Cigdem Atalayin Ozkaya, Dilek Akin. 4. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved; Cigdem Atalayin Ozkaya.
Competing interests: The authors of this manuscript certify that they have no proprietary, financial, or other personal interest of any nature or kind in any product, service, and/or company that is presented in this article. The authors declare no competing interests.
Research funding: This study was supported by the Ege University Scientific Research Projects Coordinatorship (Project No: TGA-2019-20905).
1. Komabayashi, T, Zhu, Q, Eberhart, R, Imai, Y. Current status of direct pulp-capping materials for permanent teeth. Dent Mater J 2016;35:1–12. https://doi.org/10.4012/dmj.2015-013.Search in Google Scholar PubMed 2. Kunert, M, Lukomska-Szymanska, M. Bio-inductive materials in direct and indirect pulp capping-a review article. Materials 2020;13:1204. https://doi.org/10.3390/ma13051204.Search in Google Scholar PubMed PubMed Central 3. Chen, L, Suh, B. Cytotoxicity and biocompatibility of resin-free and resin-modified direct pulp capping materials: a state-of-the-art review. Dent Mater J 2017;36:1–7. https://doi.org/10.4012/dmj.2016-107.Search in Google Scholar PubMed 4. Parirokh, M, Torabinejad, M. Mineral trioxide aggregate: a comprehensive literature review-part I: chemical, physical, and antibacterial properties. J Endod 2010;36:16–27. https://doi.org/10.1016/j.joen.2009.09.006.Search in Google Scholar PubMed 5. Malkondu, Ö, Kazandaǧ, MK, Kazazoǧlu, E. A review on biodentine, a contemporary dentine replacement and repair material. BioMed Res Int 2014:160951. https://doi.org/10.1155/2014/160951.Search in Google Scholar PubMed PubMed Central 6. Arora, V, Nikhil, V, Sharma, N, Arora, P. Bioactive dentin replacement. IOSR JDMS 2013;12:51–7.10.9790/0853-1245157Search in Google Scholar 7. About, I. Biodentine: from biochemical and bioactive properties to clinical applications. G Ital Endod 2016;30:81–8. https://doi.org/10.1016/j.gien.2016.09.002.Search in Google Scholar 8. Gandolfi, MG, Siboni, F, Prati, C. Chemical-physical properties of TheraCal LC, a novel light-curable MTA-like material for pulp capping. Int Endod J 2012;45:571–9. https://doi.org/10.1111/j.1365-2591.2012.02013.x.Search in Google Scholar PubMed 9. Kamal, E, Nabih, S, Obeid, R, Abdelhameed, M. The reparative capacity of different bioactive dental materials for direct pulp capping. Dent Med Probl 2018;55:147–52. https://doi.org/10.17219/dmp/90257.Search in Google Scholar PubMed 10. Jeanneau, C, Laurent, P, Rombouts, C, Giraud, T, About, I. Light-cured tricalcium silicate toxicity to the dental pulp. J Endod 2017;43:2074–80. https://doi.org/10.1016/j.joen.2017.07.010.Search in Google Scholar PubMed 11. Holiel, AA, Mahmoud, EM, Abdel-Fattah, WM, Kawana, KY. Histological evaluation of the regenerative potential of a novel treated dentin matrix hydrogel in direct pulp capping. Clin Oral Invest 2021;25:2101–12. https://doi.org/10.1007/s00784-020-03521-z.Search in Google Scholar PubMed 12. Ravindran, S, Gao, Q, Ramachandran, A, Sundivakkam, P, Tiruppathi, C, George, A. Expression and distribution of grp-78/bip in mineralising tissues and mesenchymal cells. Histochem Cell Biol 2012;138:113–25. https://doi.org/10.1007/s00418-012-0952-1.Search in Google Scholar PubMed PubMed Central 13. Smith, AJ, Murray, PE, Sloan, AJ, Matthews, JB, Zhao, S. Trans-dentinal stimulation of tertiary dentinogenesis. Adv Dent Res 2001;15:51–4. https://doi.org/10.1177/08959374010150011301.Search in Google Scholar PubMed 14. Magloire, H, Romeas, A, Melin, M, Couble, ML, Bleicher, F, Farges, JC. Molecular regulation of odontoblast activity under dentin injury. Adv Dent Res 2001;15:46–50. https://doi.org/10.1177/08959374010150011201.Search in Google Scholar PubMed 15. Kim, YK, Kim, SG, Byeon, JH, Lee, HJ, Um, IU, Lim, SC, et al.. Development of a novel bone grafting material using autogenous teeth. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:496–503. https://doi.org/10.1016/j.tripleo.2009.10.017.Search in Google Scholar PubMed 16. Chen, J, Cui, C, Qiao, X, Yang, B, Yu, M, Guo, W, et al.. Treated dentin matrix paste as a novel pulp capping agent for dentin regeneration. J Tissue Eng Regen Med 2017;11:3428–36. https://doi.org/10.1002/term.2256.Search in Google Scholar PubMed 17. Sedek, EM, Kamoun, EA, El-Deeb, NM, Abdelkader, S, Fahmy, AE, Nouh, SR, et al.. Photocrosslinkable gelatin-treated dentin matrix hydrogel as a novel pulp capping agent for dentin regeneration: I. synthesis, characterisations and grafting optimisation. BMC Oral Health 2023;23:536. https://doi.org/10.1186/s12903-023-03236-z.Search in Google Scholar PubMed PubMed Central 18. Qureshi, A, Soujanya, E, Nandakumar, P, Pratap Kumar, M, Sambashiva Rao, P. Recent advances in pulp capping materials: an overview. J Clin Diagn Res 2014;8:316–21. https://doi.org/10.7860/JCDR/2014/7719.3980.Search in Google Scholar PubMed PubMed Central 19. Mente, J, Hufnagel, S, Leo, M, Michel, A, Gehrig, H, Panagidis, D, et al.. Treatment outcome of mineral trioxide aggregate or calcium hydroxide direct pulp capping, long-term results. J Endod 2014;40:1746–51. https://doi.org/10.1016/j.joen.2014.07.019.Search in Google Scholar PubMed 20. Yasuda, Y, Ogawa, M, Arakawa, T, Kadowaki, T, Saito, T. The effect of mineral trioxide aggregate on the mineralisation ability of rat dental pulp cells: an invitro study. J Endod 2008;34:1057–60. https://doi.org/10.1016/j.joen.2008.06.007.Search in Google Scholar PubMed 21. Bortoluzzi, EA, Niu, LN, Palani, CD, El-Awady, AR, Hammond, BD, Pei, DD, et al.. Cytotoxicity and osteogenic potential of silicate calcium cements as potential protective materials for pulpal revascularisation. Dent Mater 2015;31:1510–22. https://doi.org/10.1016/j.dental.2015.09.020.Search in Google Scholar PubMed PubMed Central 22. Gomes, AC, Gomes-Filho, JE, Oliveria, S. Mineral trioxide aggregate stimulates macrophages and nast cells to release neutrophil chemotactic factors: role of IL-1 beta, MIP-2 and LTB (4). Oral Surg Oral Med Oral Pathol Oral Radiol Endod 2010;109:135–42.10.1016/j.tripleo.2009.08.025Search in Google Scholar PubMed 23. Luo, Z, Li, D, Kohli, MR, Yu, Q, Kim, S, He, WX. Effect of Biodentine™ on the proliferation, migration and adhesion of human dental pulp stem cells. J Dent 2014;42:490–7. https://doi.org/10.1016/j.jdent.2013.12.011.Search in Google Scholar PubMed 24. Singh, S, Ansh*ta, D, Ravichandiran, V. MCP-1: function, regulation, and involvement in disease. Int Immunopharm 2021;101:107598. https://doi.org/10.1016/j.intimp.2021.107598.Search in Google Scholar PubMed PubMed Central 25. Bhavsar, I, Miller, CS, Al-Sabbagh, M. Macrophage inflammatory protein-1 alpha (MIP-1 alpha)/CCL3: as a biomarker. In: General Methods in Biomarker Research and Their Applications. Dordrecht: Springer; 2015, 1:223–49 pp.10.1007/978-94-007-7696-8_27Search in Google Scholar 26. Giraud, T, Jeanneau, C, Rombouts, C, Bakhtiar, H, Laurent, P, About, I. Pulp capping materials modulate the balance between inflammation and regeneration. Dent Mater 2019;35:24–35. https://doi.org/10.1016/j.dental.2018.09.008.Search in Google Scholar PubMed 27. Diamanti, E, Mathieu, S, Jeanneau, C, Kitraki, E, Panopoulos, P, Spyrou, G, et al.. Endoplasmic reticulum stress and mineralisation inhibition mechanism by the resinous monomer HEMA. Int Endod J 2013;46:160–8. https://doi.org/10.1111/j.1365-2591.2012.02103.x.Search in Google Scholar PubMed 28. Poggio, C, Beltrami, R, Colombo, M, Ceci, M, Dagna, A, Chiesa, M. In vitro antibacterial activity of different pulp capping materials. J Clin Exp Dent 2015;7:e584–8. https://doi.org/10.4317/jced.52401.Search in Google Scholar PubMed PubMed Central 29. Araújo, LB, Cosme-Silva, L, Fernandes, AP, de Oliveira, TM, Cavalcanti, BN, Filhu, JEG, et al.. Effects of mineral trioxide aggregate, Biodentine and calcium hydroxide on viability, proliferation, migration and differentiation of stem cells from human exfoliated deciduous teeth. J Appl Oral Sci 2018;26:e20160629. https://doi.org/10.1590/1678-7757-2016-0629.Search in Google Scholar PubMed PubMed Central 30. Kim, RJ, Kim, MO, Lee, KS, Lee, DY, Shin, JH. An invitro evaluation of the antibacterial properties of three mineral trioxide aggregate (MTA) against five oral bacteria. Arch Oral Biol 2015;60:1497–502. https://doi.org/10.1016/j.archoralbio.2015.07.014.Search in Google Scholar PubMed 31. Deshpande, P, Nainan, MT, Metta, KK, Shivanna, V, Ravi, R, Prashanth, BR. The comparative evaluation of antibacterial activity of methacryloxydodecyl pyridinium bromide and non-methacryloxydodecyl pyridinium bromide dentin bonding systems using two different techniques: an invitro study. J Int Oral Health 2014;6:60–5.Search in Google Scholar 32. Miller, MB. Pulp capping materials-is there anything better than Dycal. Gen Dent 2013;61:10–1.Search in Google Scholar 33. Koruyucu, M, Topcuoglu, N, Tuna, EB, Ozel, S, Gencay, K, Kulekci, G, et al.. An assessment of antibacterial activity of three pulp capping materials on Enterococcus faecalis by a direct contact test: an invitro study. Eur J Dermatol 2015;9:240–5. https://doi.org/10.4103/1305-7456.156837.Search in Google Scholar PubMed PubMed Central 34. Torabinejad, M, Hong, CU, Pitt Ford, TR, Kettering, JD. Antibacterial effects of some root end filling materials. J Endod 1995;21:403–6. https://doi.org/10.1016/s0099-2399(06)80824-1.Search in Google Scholar PubMed 35. Kaur, M, Singh, H, Dhillon, JS, Batra, M, Saini, M. MTA versus Biodentine: review of literature with a comparative analysis. J Clin Diagn Res 2017;11:1–5. https://doi.org/10.7860/JCDR/2017/25840.10374.Search in Google Scholar PubMed PubMed Central References
Supplementary Material
This article contains supplementary material (https://doi.org/10.1515/tjb-2024-0040).
Received: 2024-02-09
Accepted: 2024-07-05
Published Online: 2024-09-04
© 2024 the author(s), published by De Gruyter, Berlin/Boston
This work is licensed under the Creative Commons Attribution 4.0 International License.
