TMR-MTA CEMENT Product Report

Transcription

1 From Production Skills to Scientific Knowledge, and onward to Fusion with Medical Science TMR-MTA CEMENT Product Report Edited by YAMAKIN Ph.D. Group

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3 Index 1. What is MTA Cement? 1.1 Features of MTA Cement 1.2 Mechanism of Setting Reaction 1.3 Usage Instructions Comparison with Calcium Hydroxide Preparation 5 3. Features of TMR-MTA CEMENT 3.1 Story of Development 3.2 Usability 3.3 Setting Time and Self-Setting Ability 3.4 Compressive Strength 3.5 Effect of Promoting Hard Tissue Formation 3.6 Bismuth Free 3.7 Biological Safety Color Change of MTA Cement by Exposure to Light Handling Procedure 5.1 Handling Steps 5.2 Handling Time and Initial Setting Time Depending on Moisture Ratio 5.3 Evaluation of Washout Resistance Product Line-up 14

4 TMR-MTA CEMENT Product Report Kato, T. (Ph.D. in Engineering); Executive Officer, Head Researcher, Development Department Mizobuchi, S. (M.S. in Science); Project Leader, Senior Researcher, Development Department Sato, Y. (Ph.D. in Business Management); Senior Chief Marketing Researcher, Public Relations Marketing Strategy Office 1. What is MTA Cement? The general term MTA cement refers to dental pulp capping material. It is used for medical treatment or protection of pulp in cases where pulp exposure is caused by cavity preparation or caused incidentally. (Figure 1) The abbreviation MTA stands for Mineral Trioxide Aggregate. Generally, bismuth oxide is added to the mineral trioxide aggregate to obtain radiopacity. Some people misunderstand MTA cement as being used for luting or bonding, since glass ionomer cement and resin cement are well-known cements in the dental field. Main component which MTA cement contains such as tricalcium silicate or dicalcium silicate is similar to Portland cement, which is used as a building material for construction, etc.; This is why MTA cement is referred to as cement. In the Japanese dental market, MTA cement was first launched by Dentsply in April, In foreign countries, it is used for not only pulp capping but also for various clinical cases such as perforation repair and root-end filling. Caries Pulp Exposure MTA cement Pulp Removing Caries Filling MTA cement Figure 1. Example of Pulp Capping Using MTA cement 1.1 Features of MTA cement The merits of treatment using MTA cement are summarized in Table 1. The operational method is very easy: simply make the material paste by mixing powder and water, and cap the exposed pulp. 2

5 Table 1. The Merits of Treatment Using MTA cement Setting by Mixing with Water MTA cement is set by being mixed with water, making it suitable for use in the intraoral area. Sealing Ability As MTA cement expands slightly while it is set, restrains leakages at the microscopic level are inhibited, preventing bacterial infection. Biocompatibility (Effect of Promoting Hard Tissue Formation) The cytotoxicity of MTA cement is lower than that of other dental cements, and MTA cement promotes the formation of new dentine. Disinfectant Ability MTA cement shows strong alkalinity (ph 12) during the setting process, it disinfects the adhering and surrounding bacteria. Regenerating Tooth Material MTA cement promotes the formation of hydroxyapatite, which is a constituent of teeth, by releasing CA 2+ at the dentinal tubules. Preserving Dental Nerves MTA cement enables treatment to proceed leaving nerves undisturbed, extending the life of teeth. After setting, MTA cement prevents the recurrence of caries by its sealing ability; moreover, it deters bacteria and demonstrates antibacterial ability caused by strong alkalinity of calcium hydroxide, which is generated by reacting with water. (Figure 2) Also, calcium ion in the component is released then hydroxyapatite is formed around it; moreover, the formation of new dentine will be promoted by the high biocompatibility. 2(3CaO SiO 2 ) + 6H 2 O 3CaO 2SiO 2 3H 2 O + 3Ca(OH) 2 Tricalcium Silicate Water Calcium Silicate Hydrate Calcium Hydroxide 2(2CaO SiO 2 ) + 4H 2 O 3CaO 2SiO 2 3H 2 O + Ca(OH) 2 Dicalcium Silicate Water Calcium Silicate Hydrate Calcium Hydroxide Figure 2. Hydration Reaction of MTA cement Shows antibacterial ability caused by strong alkalinity Thanks to these effects, nerves can be protected even with pulp exposure; as a result, treatment can be done preserving the pulp as much as possible. Especially in the field of pediatric dentistry, there is a strong need for MTA cement as pulpectomy will affect the formation of permanent tooth substance. 1.2 Mechanism of Setting Reaction The mechanism of setting reaction by mixing MTA cement and water is as follows: 1) Hydration reaction occurs on surfaces of cement particles and hydrate crystals are extracted on the surfaces. 2) Setting reaction starts slowly as hydrate crystals on the surfaces of cement and surrounding hydrate crystals become interlocked. Regarding the hydration reaction which is shown in Figure 3, if the amount of water is insufficient, the density of hydrate crystals becomes low and coupling between particles will be weaker; as a result, setting will be insufficient. 1) However, if too much water is added, the excess water, which will not affect the hydration reaction, will lower the compressive strength, because the number of spaces inside the cement will increase; therefore, avoid adding too much water. 1) Also, the particle diameter and surface area differ depending on the product; so, the moisture ratio has to be adjusted in each case, based on the recommended moisture ratio given by the manufacturer. 3

6 Bonding water for hydration reaction will adhere to a cement particle. Hydrate crystals are generated by the hydration reaction of the bonding water and a cement particle. The strength will be exhibited by the hydrate crystals being dense and interlocked with each other. Bonding water Excess water In cases where moisture is sufficient Cement particle Cement particle The bonding water evaporates The number of hydrate crystals decreases The low number of hydrate crystals causes lowering of the strength. In cases where the moisture is insufficient Cement particle Cement particle Figure 3. The Difference in Hydration Reaction Caused by the Amount of Water 1.3 Usage Instructions The steps for direct pulp capping are as follows: 1) Clinical Case 1 1. Before Treatment 2. Pulp Exposure 3. Capping Pulp with TMR-MTA CEMENT Figure 4. Usage Instructions for MTA cement, Case 1: Direct Pulp Capping Photos provided by: Division of Periodontology and Endodontology School of Dentistry, Health Sciences University of Hokkaido 2) Clinical Case 2 1. Before Treatment 2. Pulp Exposure 3. Capping Pulp with TMR-MTA CEMENT Figure 5. Usage Instructions for MTA cement, Case 2: Vital Pulp Therapy Photos provided by: Division of Pediatric Dentistry, Health Sciences University of Hokkaido 4

7 2. Comparison with Calcium Hydroxide Preparation Generally, calcium hydroxide preparation is used as pulp capping material. It exhibits hard tissue inducing action and disinfectant ability caused by strong alkalinity; moreover, the price is about one fourth (1/4) to one twentieth (1/20) of MTA cement; therefore, it is used for various dental treatments. However, there are 3 weak points compared with MTA cement, as follows: The material becomes deteriorated as ingredients are eluted easily. Sealing ability becomes lower caused by elution, increasing the risk of bacterial infection from the margins in the long term. Strength is weak, as it does not set. There is data on long-term prognosis. In the case of pulp capping with MTA cement, the probability of success is maintained at about 80% after one to three years. On the other hand, it is reported that in the case of using calcium hydroxide preparation, the probability of success after one year is 75%, which is roughly equal to MTA cement; however, it becomes 55% after 2 years and drops to about 45% after 3 years. 2) For conservative treatment, stability in the long term is indispensable; therefore, MTA cement is the material which benefits patients. 5

8 3. Features of TMR-MTA CEMENT 3.1 Story of Development Development started taking advantage of our meeting Prof. Kazuhiko Endo Ph.D., Division of Biomaterials and Bioengineering, Department of Oral Rehabilitation, School of Dentistry, Health Sciences University of Hokkaido in October 2011 at the Japanese Society for Dental Materials and Devices in October Prof. Endo had already started basic research on MTA cement with Prof. Masato Saitoh Ph.D., Division of Pediatric Dentistry, School of Dentistry, Health Sciences University of Hokkaido. In the field of pediatric dentistry, there was a need for MTA cement to preserve nerves because baby teeth are small and caries tend to go near the nerve. However, most MTA cements are foreign products and not user-friendly, so there was a demand for products with good usability. YAMAKIN shared Prof. Endo and Prof. Saitoh s vision, and so joint development started. The development process didn t go smoothly. Many difficulties had to be faced and overcome before the product was finally launched in July It took about 6 years to develop from the beginning Usability To improve its usability, spherical-silica fine particles and zirconia fine particles are added to TMR-MTA CEMENT. As a result, it is easy to mix it with a small amount of water. The bearing effect of the spherical-silica fine particles improves the product s fluidity. This enables users to make an even paste easily with a small amount of water in a short time. (Figure 6) Spherical-silica fine particle Calcium silica particle Zirconia fine particle Improving fluidity Figure 6. Image of Bearing Effect 3. 3 Setting Time and Self-Setting Ability As discussed above, TMR-MTA CEMENT mixes well to an even paste with a small amount of water. Since it can be mixed with a small amount of water, its designed setting time is short, so that the initial setting is completed in 15 to 30 min. when the moisture ratio is 20%. When the amount of moisture is less, the setting time will be about 5 to 10 min. (Figure 7) Also, it is possible to make the initial setting time shorter by removing excess moisture. The initial setting time is measured in accordance with the measurement of setting time in ISO 6876:2001. To be specific, the setting time is the required time for setting until a Vicat needle does not leave a mark on the surface of cement when a load weight of 100±0.5g is applied to the Vicat needle and the diameter of the tip is 2±0.1 mm. However, this initial setting time is the required time for setting to a certain degree, not for setting completely by hydration reaction. It is equivalent to the setting time for industrial cement. 3) After the 6

9 initial setting, hydration reaction of TMR-MTA CEMENT progresses in earnest and the strength increases; therefore, the compressive strength is measured 1 to 7 days later after it has set sufficiently (min) Setting time Moisture ratio (%) Figure 7. Setting Time Depending on the Moisture Ratio 3. 4 Compressive Strength Completion of the setting can be evaluated by measuring the compressive strength. (Figure 8) In general, a moistened cotton pellet needs to be placed on MTA cement after covering exposed pulp with MTA cement to replenish the moisture, and the final filling is done one day later. As shown in Figure 8, TMR- MTA CEMENT achieves high compressive strength which is equivalent with the one kept in water after setting, even though it is kept in air. 4) This means that TMR-MTA CEMENT sets sufficiently without any need to replenish the moisture with a cotton pellet after application, so the final filling using composite can be done on the same day and TMR-MTA CEMENT can reduce the burden on the patient. Since it sets quickly, TMR-MTA CEMENT achieves high compressive strength, about 90 MPa from one day after application if the moisture ratio is 20%. (Figure 9) This compressive strength reaches about 140MPa after a week, equivalent to the compressive strength of glass ionomer cement; therefore, the strength is sufficient to protect the pulp. The physical properties of MTA cement are increased when the moisture ratio is lower, and decrease when the moisture ratio is higher. 5) The compressive strength of TMR-MTA CEMENT exhibits the same trend when the moisture ratio is 18, 20 and 23%. 6) 120 Compressive Strength (MPa) Kept in water Kept in air Figure 8. The Compressive Strength of TMR-MTA CEMENT 1 Day After Mixing 4) Moisture Ratio 20% 7

10 1 Day Later 1 Week Later (MPa) Compressive Strength Moisture Ratio (%) Figure 9. The Compressive Strength of TMR-MTA CEMENT Depending on Moisture Ratio, 1 Day and 1 Week After Mixing 6) 3. 5 Effect of Promoting Hard Tissue Formation New formation of dentine is confirmed, with odontoblast-like cells arrayed in a fence-like formation 1 week after direct pulp capping with TMR-MTA CEMENT. Figure 10. Formations of Reparative Dentine After Pulp Capping (Posterior Tooth of Rat, After 1 Week) Photos provided by: Health Sciences University of Hokkaido 3. 6 Bismuth Free General MTA cement contains bismuth oxide as a material for radiopacity but the bismuth oxide sometimes turns black caused by exposure to light. Detailed information is given in Chapter 4. On the other hand, TMR-MTA CEMENT contains zirconia, which is used as a material for radiopacity for various biological cases, such as in dental materials and joint prosthesis. Zirconia is a chemically stable substance, so color change of TMR-MTA CEMENT is unlikely to happen. 8

11 3.7 Biological Safety TMR-MTA CEMENT is designed with concern for biological safety, for example using as a material for radiopacity which is made from zirconia and is chemically stable. Cytotoxicity test using V79 cell, Chinese hamster lung fibroblast was done conforming to the international standard ISO Biological evaluation of medical devices -Part 5: Tests for in vitro cytotoxicity. (Figure 11) Figure 11. V79 Cells Using a cell culture solution, prepare an extract from the material for this test. V79 cells are cultured in the prepared solution and the cytotoxicity of the material is evaluated by the number of formed cell colonies. (Figure 12) No Toxicity Toxic Figure 12. V79 Cell Colony V79 cells were cultured in extract from TMR-MTA CEMENT and the number of formed cell colonies was counted. As shown in Figure 13, at about 80%, a high formation rate of cell colonies was exhibited, even the concentration of extract was 100%. When formation rate of cell colonies is over 70% in an extract whose concentration is 100%, the evaluation of the cytotoxicity test is No cytotoxicity. Formation Rate of Cell Colonies (%) Concentration of Test Solution (%) Figure 13. Colony Formation of V79 Cells in TMR-MTA CEMENT Extract 9

12 4. Color Change of MTA Cement by Exposure to Light Purpose MTA cement has excellent features such as disinfectant ability, sealing ability, biocompatibility and effect of promoting hard tissue formation, and it is used for direct pulp capping. However, color change is reported as a problem over time. 5) This problem is caused by adhesion of blood caused by insufficient hemostasis, reaction with sulfur in protein, and blackening by reduction reaction of bismuth oxide, caused by exposure to ultraviolet rays under conditions of no oxygen. 5) To prevent blackening, zirconium oxide is added to TMR-MTA CEMENT as a material for radiopacity instead of bismuth oxide. Verification of blackening of MTA cement caused by exposure to light was carried out. 7) Materials and Methods 1) Zirconium oxide and bismuth oxide were filled into silicon molds. The visual evaluations of shade, depending on whether glycerin was applied or not applied, were carried out after the test specimens were exposed to ultraviolet rays using a UV light: MHF-0100LR, MORITEX corporation. 2) TMR-MTA CEMENT, which contains 20% of the zirconium oxide in refined white Portland cement and sample MTA cement, which contains 20% of the bismuth oxide in refined white Portland cement, were prepared, mixed with water at a moisture ratio of 20%. The materials were filled into silicon molds, glycerin was immediately applied, and then the visual evaluation of shades was conducted after exposure to LED light: G-light prima II, GC Corporation. Result and Consideration Pictures of zirconium oxide and bismuth oxide before and after being exposed to ultraviolet rays. (Figure 14) The color of the zirconium oxide was not changed by the ultraviolet rays. Bismuth oxide did not change color when glycerin was not applied, but the color turned black when the glycerin was applied. It is considered that the reason for the blackening is oxygen deficiency of bismuth oxide caused by reduction reaction by exposure to ultraviolet rays under conditions of no oxygen. UV Light Irradiation Time Test Specimen 0 min. 15 min. 30 min. With Glycerin Application Zirconium Oxide Bismuth Oxide Without Glycerin Application Zirconium Oxide Bismuth Oxide Figure 14. Comparing Color Change caused by Irradiation of Ultraviolet Rays of Zirconium Oxide and Bismuth Oxide 10

13 Pictures of TMR-MTA CEMENT containing zirconium oxide and sample MTA cement containing bismuth oxide at lengthening irradiation times under LED light are shown. (Figure 15) The color of TMR-MTA CEMENT containing zirconium oxide did not change caused by irradiation by LED light. However, the sample MTA cement containing bismuth oxide blackened more as the irradiation time became longer. Irradiation time by LED Light 0 sec. 10 sec. 30 sec. 90 sec. White Light Ivory Prototype containing 20% of Bismuth oxide Note: Verification under conditions of no oxygen obtained by the application of glycerin Figure 15. Comparing Color Change by LED Irradiation of TMR-MTA CEMENT and Sample MTA Cement Containing Bismuth Oxide Summary Bismuth oxide turns black by being exposed to light under conditions of no oxygen obtained by the application of glycerin, and sample MTA cement containing bismuth oxide also turns black by being exposed to light. On the other hand, MTA cement containing zirconium oxide does not change color by being exposed to light. 11

14 5. Handling Procedure 5. 1 Handling Steps Mix the powder and liquid according to the standard ratio, and adjust the ratio depending on the case. Since the material contacts the nerve directly, make sure to use sterilized instruments and purified water. If using metallic instruments, pay attention not to use them with too much force, because metal may shave off and cause blackening. The handling steps are shown in Figure 16. 1) Place the product (powder) on a dental mixing paper or a mixing glass pad. 2) Drip an appropriate amount of purified water near the powder. The standard ratio of powder and liquid is 0.05 g of liquid against 0.2 g of powder (moisture ratio: 20%). The purified water should be sterile. 3) Mix the powder and purified water with a spatula etc. for about 30 sec. to make it into an even paste form. 4) Cap the exposure site with the mixed material using an instrument etc. (Handling time / Approx. 3 min. after mixing) Note: Mixing strongly when using a metallic spatula causes the metal to peel off and the paste to turn black. Figure 16. How to Mix TMR-MTA CEMENT with Purified Water Method of Temporary Filling Since TMR-MTA CEMENT can be mixed with a small amount of water and sets quickly, temporary filling with glass ionomer cement can be performed right after capping the exposure site with TMR-MTA CEMENT paste and removing excess paste and moisture with a cotton pellet Handling Time and Initial Setting Time Depending on Moisture Ratio The standard moisture ratio of TMR-MTA CEMENT is 20%; however, if the paste is hard or dry and difficult to handle, the viscosity of the paste can be adjusted by adding water before the set starts. Also, the viscosity and the handling time can be adjusted by making the moisture ratio 25-30%, as shown in Table 2. 12

15 Table 2. Handling Time and Initial Setting Time Depending on Moisture Ratio Moisture Ratio (Powder : Water) State of Paste Handling Time Initial Setting Time 20% (0.2g : 0.05g) Hard About 3 min min. 25% (0.2g : 0.07g) Soft About 6 min min. 30% (0.2g : 0.09g) Very Soft About 9 min min. However, the initial setting time will be longer in the case when the exposure site is capped with soft paste. The initial setting time can be shortened by removing excess moisture using a dry cotton pellet after filling as shown in Table 3. Table 3. Moisture Ratio and Initial Setting Time Depending on Removal of Moisture Moisture Ratio 20% 25% 30% Without Wiping Moisture 15 min. 30 min. 60 min. Wiping Moisture 5 min. 5 min. 10 min Evaluation of Washout Resistance Rinsing cement with water after capping pulp with TMR-MTA CEMENT causes cement washout, dissolving and flow-away; therefore, a moist cotton pellet etc. is recommended to use to remove excess cement instead of rinsing with water. However, the required time until washout ceases to happen was measured on the assumption that rinsing with water is required. For the test 8), TMR-MTA CEMENT was filled into a hole with a diameter of 1mm and a depth of 2 mm on an acrylic board; the cement was rinsed using a three-way syringe for dental-chair use. The cement was rinsed for 3 seconds at 1 cm from the water nozzle and it was visually confirmed whether it remained or not. The cement was divided into 2 groups (cement which remained in the hole and cement which did not remain in the hole), and the results were evaluated, with a or an respectively. Where the moisture ratio was 20% or 25%, washout did not happen from15 min. after filling, and where the moisture ratio is 30%, washout did not happen from 20 min. after filling. In this evaluation, the required time to avoid washout was measured on the assumption that the rinsing time is 3 sec. Since the cement does not set completely within the time range, it should be noted that washout and decrease of strength will be caused by longer rinsing time. Table 4. Required Time and Washout Resistance (3 Sec.) Depending on Moisture Ratio Required Time 20% 25% 30% 60 min. 45 min. 30 min. 20 min. 15 min. 10 min. 5 min. 13

16 6. Product Line-up There are 2 kinds: the microtube type for ease of use and the container type for big volume. There are 2 shades, White and Ivory in the line-up, and the choice of shade depends on the case. Dental pulp capping material 2 colors - White and Light Ivory - are available! White Color Type Light Ivory Container Type 3g Microtube Type for ease of use 0.2g 3pcs LINEUP Product name TMR-MTA Cement (White, Light Ivory) Content 0.2g x 3 3g Type of Packing Micro tubes Glass Container [Adaptation] This product is intended to be used for pulp exposure of non-infected tooth pulp with a size of 2mm, in cases where pulp exposure is caused by cavity preparation or caused incidentally. Figure 17. Product Line-up of TMR-MTA CEMENT Manufactured by Otani, Kamibun, Kagami-cho, Konan-shi, Kochi, Japan 14

17 References 1) Okiji, T. (ed.) : MTA, Basic Principles and Clinical Applications (MTA sono kiso to rinshou), HYORON Publishers, Tokyo, ) Mente, J.: Mineral trioxide aggregate or calcium hydroxide direct pulp capping: an analysis of the clinical treatment outcome, J Endod 36(5), pp , ) Kobayashi, K.: The Latest Concrete Technology (Saishin konkurito kougaku), 5th ed.: MORIKITA PUBLISHING CO., LTD., Tokyo, ) The 144th Meeting of the Japanese Society of Conservative Dentistry, p.114, ) Fridland, M., Rosado, R.: Mineral trioxide aggregate solubility and porosity with different water-to-powder ratios, J Endod 29, pp , ) The 145th Meeting of the Japanese Society of Conservative Dentistry, p.129, ) The 146th Meeting of the Japanese Society of Conservative Dentistry, p.141, ) Kitamura, K.: Three Necessary Devices for Endodontic Procedures (Shinai ryouhou no sanshu no jingi): Dental Diamond Co., Tokyo, 2016.

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19 Previously Published Technical Reports Technical Report on ZEO CE LIGHT (Aug. 2002) Technical Report on Luna-Wing (May 2007) Technical Report on TWiNY ( Jul. 2010) Previously Published Safety Test Reports Vol. 1 Pursuing International Standards in Quality and Safety (Dec. 2004) Vol. 2 ZEO METAL Series Elution Test and in Vitro Cytotoxicity Test (Jun. 2005) Vol. 3 Elution Test and in Vitro Cytotoxicity Test of Precious-Metal Alloys and Gold Alloys for Metal Ceramic Restoration Use (Dec. 2005) Vol. 4 Biological Evaluation of Luna-Wing ( Jun. 2006) Vol. 5 Report on Physical Properties and Safety of High-Carat Gold Alloys (Oct. 2007) Vol. 6 Examination of the Biological Impact of the Physical Properties of Dental-Material Alloys and Gold Alloys for Hard Resin and Metal Ceramic Restoration Use (May 2008) Vol. 7 Report on the Physical Properties and Safety of the Gold Alloy Nexo-Cast (Oct. 2008) Vol. 8 Biological Evaluation of the Hybrid Composite Resin, TWiNY ( Jun. 2010) Vol. 9 Chemical and Biological Characteristics of Precious-Metal Alloys: Elution Characteristics Produced Through Mixture with Titanium (Feb. 2011) Vol. 10 Physical Properties and Safety of the Precious-Metal Alloy for Metal Ceramic Restoration Use Brightis (Oct. 2011) Vol. 11 Physical Properties and Safety of the Dental Adhesive, Multi Primer (Mar. 2014) Vol. 12 Safety of the Dental Pulp Capping Material, TMR-MTA CEMENT ( Jan. 2018) Previously Published Macromolecule Technology Reports Vol. 1 The Polymerization of Dental Materials: The Basis of Radical Polymerization (1) (Oct. 2009) Vol. 2 The Polymerization of Dental Materials: The Basis of Radical Polymerization (2) (Feb. 2010) Vol. 3 The Polymerization of Dental Materials: Restoration-Material Monomers (1) (Mar. 2010) Vol. 4 The Polymerization of Dental Materials: Restoration-Material Monomers (2) ( Jul. 2010) Vol. 5 The Polymerization of Dental Materials: The Influence of Oxygen (Aug. 2011) Vol. 6 The Polymerization of Dental Materials: Primers and Developers (Oct. 2012) Vol. 7 Polymerization Silane Coupling Agent: Methacrylic Resin (Acrylic Resin) ( Jun. 2013) Vol. 8 Shrinkage of Dental Composite in Polymerization (Nov. 2014) Vol. 9 Application of Iodonium Salt as Initiator Component in Dental Material (Mar. 2017) All Previously Published Science Reports Vol. 1 Dental Surgery and Bisphosphonate Formulation (Aug. 2010) Vol. 2 Reactive Oxygen: Its Generation, Elimination and Effects (Nov. 2011) Vol. 3 The Hypoxic World ( Jul. 2012) Vol. 4 Recent Progress in the Regeneration of Tooth Material (Feb. 2014) Vol. 5 Application of Fluoride and Its Effect (Oct. 2016) Previously Published Product Reports Basic Information and Product Report on Zirconia (Feb. 2014) Basic Information and Product Report on Titanium ( Jun. 2016) Basic Information and Product Report on Hybrid Resin for CAD/CAM use (Sep. 2014) Basic Information and Product Report on Dental Restorative Material (Sep. 2015) Basic Information and Product Report on Dental Bonding Material ( Jan. 2016) Product Report on Multi Primer Series (Oct. 2017) Editor: Takahiro Kato Publisher: Shigenari Yamamoto Date of publication: 20 Apr. 2018

20 Head Office: 3-7 Sanadayama-cho Tennoji-ku Osaka , Japan Biological Science Safety Laboratory: Laboratory in the Department of Oral and Maxillofacial Surgery, Kochi Medical School, Kochi University Kohasu, Oko-cho, Nankoku-shi, Kochi , JAPAN Branch Office: Tokyo, Osaka, Sendai, Nagoya, Fukuoka, JAPAN P: F: E: INTERNATIONAL